Bronchopulmonary Disease in the Cat: Historical, Physical,
Radiographic, Clinicopathologic, and Pulmonary Functional
Evaluation of 24 Affected and 15 Healthy Cats
Janice A. Dye, Brendan C. McKiernan, Elizabeth A. Rozanski, Walter E. Hoffrnann, J o h n M. Losonsky,
Linda D. Homco, Rita M. Weisiger, and lbulaimu Kakoma
The results of clinical and pulmonary functional evaluation
of 24 cats with bronchopulmonary disease and 15 healthy
cats are presented. Affected cats had historical evidence of
excessive reflexes (coughing, sneezing); physical evidence
of airway secretions (crackles), obstruction (wheezing), and
increased tracheal sensitivity; radiographic evidence of bron-
chial and interstitial lung disease; and cytological evidence
of airway inflammation or mucous secretions. Bacterial iso-
lates from healthy and affected cats were predominantly
Gram-negative rods, indicating that bronchi of cats are not
always sterile and that normal flora should be considered
in interpreting cultures from cats with suspected broncho-
pulmonary disease. Cats were grouped according t o relative
disease severity based on scored historical, physical, and
radiographic abnormalities. The mean (? standard devia-
tion) baseline lung resistance measurement in healthy cats
was 28.9 cm H,O/L/s (?6.2 cm H,O/L/s), whereas in mildly,
B ronchopulmonary disease in the cat represents a group
of poorly understood airway and alveolar space
disorder^.'.^ Clinical signs are thought to be due, in part, to
underlying airway obstruction. Factors contributing to the
development of airway obstruction presumably include de-
velopment of airway inflammation and mucosal edema, de-
velopment of airway smooth muscle hypertrophy and con-
striction, and excessive production or retention of pulmonary
secretions. Actual measurements of pulmonary function in
cats with bronchopulmonary disease have not been available
previously. We obtained pulmonary functional measure-
ments from cats with naturally occurring disease and from
clinically healthy cats in an attempt to better assess the pres-
ence and degree of airway obstruction in affected cats.
Healthy cats were defined as subjects with no known histori-
cal or physical findings indicating respiratory disease. A
complete clinical database (including historical, physical,
and radiographic assessments) was obtained for all cats and
also was used to quantify the relative clinical severity of
respiratory disease. Measurements of baseline lung resis-
tance (RL) and dynamic lung compliance (Cdyn)were ob-
tained, and airway cytological and microbial culture data
were collected. Whenever possible, evaluation also included
IV administration of a bronchodilator (BD) to assess revers-
ibility of the airway obstruction, or alternatively, an aerosol-
ized bronchoprovocative challenge to assess the ease with
which airway obstruction could be induced (ie, the degree
of airway responsiveness [AR] present).
Materials and Methods
Cats
Twenty-four cats with naturally occurring bronchopulmonary dis-
ease and 15 clinically healthy cats were evaluated in a cross-sectional
study conducted over a 1-year period. The cats with bronchopulmo-
nary disease included 21 cats presented or referred to the University
of Illinois Veterinary Medicine Teaching Hospital (UIVMTH) for a
variety of clinical signs suggestive of lower respiratory disease. One
Journal of Veterinary Internal Medicine, Vol 10, No 6 (November-December), 1996: pp 385400
moderately, and severely affected cats it was 38.3 cm H,O/
L/s (221.5 cm H,O/L/s), 44.8 cmH,O/L/s (27.7 cm H,O/L/s),
and 105.2 cm H,O/L/s (k66.9 cm H,O/L/s), respectively. In
healthy cats, dynamic lung compliance was 19.8 (?7.4),
whereas in mildly, moderately, and severely affected cats it
was 14.7 mL/cm H,O (23.8 mL/cm H,O), 17.7 mL/cm H20
(t6.9mL/cm H,O), and 13.0 mL/cm H,O (27.9 mL/cm H,O),
respectively. Thus, airway obstruction was present in many
of the affected cats. Based on acute response t o the bron-
chodilator, terbutaline, airway obstruction was partially re-
versible in many affected cats, although the degree of revers-
ibility varied. Furthermore, based on bronchoprovocation
testing, 6 (of 7) affected cats evaluated also had increased
airway responsiveness t o aerosolized methacholine.
J Vet Intern Med 1996;10:385-400. Copyright 0 1996 by the
American College of Veterinary Internal Medicine.
subject (cat 15) was a long-term (17 months) colony cat that had
intermittent coughing at the time of evaluation. Two other cats (cats
1 and 18) were obtained directly from the Office of Laboratory
Animal Care (OLAC) facility when increased bronchial sounds and
enhanced tracheal sensitivity were detected on physical examination,
and mild to moderate bronchial patterns were observed on thoracic
radiographs. Based on physical examination and radiographic find-
ings, none of the affected cats had clinically relevant cardiovascular,
pleural space, or mediastinal disease, neither did they have upper
airway structural abnormalities. All BD medications were withheld
for at least 4 days, and corticosteroid and antibiotic therapy was
withheld for at least 2 weeks prior to evaluation.
The 15 clinically healthy cats included 6 privately owned pets
undergoing elective procedures that required anesthesia, 2 blood
donors for the UIVMTH, and 7 colony cats housed in the OLAC
facilities for 8 to I2 months prior to evaluation.
From the Department of Veterinary Clinical Medicine, Medicine
(Dye, McKiernan, Rozanski), Rudiology (Losonsky, Homco), and
Microbiology (Weisiger), Department qf Veterinary Pathobiology,
Clinical Pathology ( H o m a n n ) ,and Microbiology/lmmunology (Ka-
koma), College of veterinary Medicine, University of Illinois, Ur-
bana, IL.
Accepted May 25, 1996.
Supported in part by a grant from The Companion Animal Re-
search Funds, College of Veterinary Medicine, University of Illinois.
The authors thank Drs Bridget Hayes, Debi O’Keefe, Jennifer
Smith, Linda Wolf; and other veterinarians referring cases for this
study. Additionally, we rhank Dr Gail Scherba for pegorming the
virus isolation procedures, Drs Ron Smith and Marge Pie1 for the
occult heartworm analyses, and Dr Julie Klauer and technical sup-
port staff Duvid Piyor, Val Gates, CVT, Maria Martinez, CVT,
Kristie Stasi, CVT, und receptionist Vickie Armstrong, f o r their ex-
pertise and ussisiance on this study.
Reprint requests: Brendan C. McKiernan, DVM, Department of
Veterinary Clinical Medicine, University of Illinois, College of Vet-
erinary Medicine, 1008 W Hazelwood Dr, Urbanu, IL 60801.
Copyright 0 1996 by the American College of Veterinary Internal
Medicine
0891-6640/96/1006-0008$3.00/0
385

386
Clinical Evaluation
Evaluation consisted of an equally weighted and scored historical
questionnaire, a physical examination, and radiographic assessment.
The “combined bronchopulmonary disease score” was used to char-
acterize the cat as healthy, or as having mild, moderate, or severe
disease
History scores were based on owner-completed questionnaires in
which the frequency of coughing, wheezing, sneezing, or dyspneic
episodes was scored from rarely to more than 8 times per day.
Duration of primary complaints was coded from less than 1 week
to more than 1 year. At initial presentation, a scored physical exami-
nation was completed for each cat. Higher scores reflected the sever-
ity of adventitial lung sounds (eg. crackles, wheezes, augmented
bronchial sounds), tracheal sensitivity, decreased chest compressibil-
ity on palpation, and nasal or ocular discharge. If tracheal palpation
elicited a cough, lung sounds were rescored (eg, post-tussive crackles
or wheezes). Thoracic radiography was performed (ventrodorsal,
right and left lateral views); radiographic signs were assessed by 4
of the authors (JML, LDH, JAD, BMcK) using a blinded technique.
Higher scores corresponded with the presence and severity of the
bronchial, interstitial, and alveolar disease, as well as lung lobe
collapse, pulmonary hyperinflation, or the presence of aerophagia.
A minimum clinicopathologic database consisted of a CBC, bio-
chemical profile (creatinine, blood urea nitrogen [BUN], total pro-
tein, albumin, calcium, phosphorus, sodium, potassium, chloride,
glucose, alkaline phosphatase, alanine aminotransferase, y-glutamyl
transferase, total bilirubin, magnesium, and cholesterol determina-
tions), fecal flotation, and occult heartworm titer (Dirocheck enzyme-
linked immunosorbent assay [ELISA] antigen test; Synbiotics Corp,
San Diego, CA). Tonsilar swabs for virus isolation of rhinotracheitis
and calicivirus were performed in 6 cats with bronchopulmonary
disease that also had signs consistent with upper respiratory tract
infection (URTI).
Cats were anesthetized and intubated with a sterile endotracheal
tube for determination of pulmonary function measurements (see
below). After function testing, a double-lumen, protected catheter
brush (Microbiology Specimen Brush; Microvasive, Watertown,
MA) was used to obtain material for tracheobronchial cytology and
aerobic bacterial cultures. The brush was gently vortexed in 0.5 mL
of sterile saline, and a quantitative culture (10 pL) was performed
on this sample. A bronchial wash subsequently was performed (simi-
lar to the method described by Moise and Blue’), using I or 2 1.5-
mL aliquots of sterile saline instilled into the airways. Cytological
preparations of the samples were made using a cytocentrifuge. Slides
were stained with modified Wright’s stain (Hema-Tek Stain Pak;
Miles Inc, City, State), and differential cell counts were determined
based on 100 to 200 cells per specimen.
Pulmonary Function Equipment and
Baseline Measurements
For baseline function testing, all cats were anesthetized with thi-
amylal sodium, dosed to effect. No premedication was used. Dilute
( I :10) 2% lidocaine was sprayed onto the caudal pharynx to avoid
laryngeal spasm while cats were intubated with a uniform-length
(15-cm) cuffed endotracheal tube (4-mm interior dimension). Resis-
tance of the tube alone was determined to be 12 cm H20/L/s. Cats
were placed in sternal recumbency and allowed to breathe spontane-
ously. Excessive secretions, if present, were suctioned from the endo-
tracheal tube, care was taken to avoid contact with the trachea itself.
A preheated No. 0 Fleisch pneumotachograph (OEM Medical, Rich-
mond, VA) was connected to the endotracheal tube, and a pediatric
esophageal balloon (A&E Medical Corp, Farmingdale, NJ) was
placed in the caudal thoracic esophagus. Transpulmonary pressure
(P,p)measurements were obtained using a differential pressure trans-
ducer (Model DP45-18; Validyne, Northridge, CA) to measure the
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DYE ET AL
difference between the pleural pressure, P,, , (estimated from esopha-
geal pressure), and the airway opening pressure, Pan. Signals from
the pneumotachograph-associated differential pressure transducer
(Model DP-45-16; Validyne) were proportional to air flow. Tidal
volumes were determined by electronic integration of the flow signal.
The response characteristics of these systems were phase-matched
to 10 Hz. The R,- and Cdynmeasurements were calculated using a
pulmonary mechanics analyzer (Model 6 ; BUXCO Electronics,
Sharon, CT). At isovolume conditions, R, (cm H,O/L/s) was calcu-
lated as the difference in transpulmonary pressure divided by the
difference in flow. C,,, (mL/cmH,O) was calculated from the differ-
ence in volume divided by the difference in transpulmonary pressure
at conditions of zero flow. Measurements were collected for a 1-
minute period (encompassing 15 to 20 breaths), once the cat resumed
a stable breathing pattern after anesthetic induction and instrumenta-
tion. These measurements were averaged and used to determine the
mean baseline RL and C,,, for each cat. Breaths acquired during
movement or coughing, or those with evidence of endotracheal tube
secretions were excluded.
Acute Response to a Bronchodilator
In cats with bronchopulmonary disease, whenever possible, base-
line function testing was followed immediately by administration of
a test dose of the &adrenergic agonist terbutaline (Brethine; Geigy
Pharmaceuticals, Ardsley, NY). On a separate occasion, similar test-
ing was performed on 9 of the 1.5 healthy cats. Terbutaline, 0.01
mgkg, was administered by slow IV injection. After the injection,
additional measurements of RL and Cdynwere obtained. Measure-
ments acquired during each postinjection 1-minute interval were
averaged. After BD administration, airway responses were expressed
as both the absolute change (eg, ARL = Post BD - Pre BD) and
percentage change from baseline measurements (eg, ARL/PreBD X
100). Throughout the trial, auscultation was used to determine
changes in heart rate.
Bronchoprovocation Testing
Using increasing concentrations of 2 different aerosolized bron-
choconstrictive agonists, challenges were performed in 8 of the
healthy cats using 2 different anesthetic agents, IV thiamylal sodium
and pentobarbital sodium. Supplemental anesthetic doses were ad-
ministered as needed to maintain a relatively constant level of anes-
thesia throughout the challenge. The bronchoprovocative agonists
used were histamine and methacholine (the acetylcholinesterase-
resistant analogue of acetylcholine). In total, each healthy cat under-
went 4 separate challenges. To ensure adequate recovery between
challenges, testing was performed over a 7-month period. Provoca-
tion testing also was performed on select cats with bronchopulmo-
nary disease.
Once cats were intubated and connected to the pulmonary function
instrument, baseline RL and Cdynmeasurements were acquired for 1
minute. After baseline data acquisition, cats first were challenged
with nebulized normal saline ( 5 consecutive breaths). If exposure to
nebulized saline failed to induce significant constriction, cats subse-
quently were challenged with increasing concentrations of the ago-
nist reconstituted in saline (5 breaths per concentration). To generate
the aerosol, an o;ygen-driven (1 5 to 18 psi) collison nebulizer was
connected to the endotracheal tube, and the lungs were inflated to
an airway opening pressure of 25 cm H20. This nebulizer is reported
to produce particles with a mass median aerodynamic diameter of
2 to 4 pm.6 Once a stable breathing pattern was re-established after
aerosol administration, lung function measurements obtained during
a I-minute interval were averaged to determine the cat’s response
to the specific agonist concentration. Intervals of at least 5 minutes
were allowed between subsequent challenges. Testing was termi-
nated when RL increased to 200% of the postsaline challenge value

BRONCHOPULMONARY DISEASE IN THE CAT
(ie, effective concentration or EC2(HIRL). when Cdyndecreased to
65% of the postsaline challenge value (ie, ECh5Cdyn), or until a
concentration of 10 to 20 mg/mL of the agonist was reached, which-
ever came first. These end-points were chosen to avoid induction of
excessive bronchoconstriction that may have endangered the animal.
At the conclusion of testing, bronchoconstriction was reversed by
IV administration of either atropine or terbutaline.
Data Analysis
For the clinical evaluations, data were analyzed using a t-test
(unpaired, 2-tailed) for single comparisons or an analysis of variance
(ANOVA) with Fisher’s protected least-significance difference
(PLSD) testing for determination of multiple compari~ons.~ For base-
line RL and Cdyn measurements, the group mean, coefficient of varia-
tion (CV), and small-sample 95% confidence interval (CI) about the
mean’ were determined for the healthy cats. Baseline RL measure-
ments of the affected cats were considered abnormal if they were
above the upper 95% CI established for the group of healthy cats.
Baseline Cdynmeasurements were considered abnormal if they fell
outside the small-sample 95% CI of the healthy cats. In affected
subjects, a Pearson’s correlation coefficient ( r ) was used to assess
the degree of association between data sets (eg, RL versus physical
examination score).’
Based on the maximal change (A) in the RL or Cdynmeasurement,
ANOVA testing was used to determine differences in the acute
bronchodilatory response to terbutaline. For bronchoprovocation
testing, data collected during the I-minute interval after each 5-
breath aerosol challenge were used to construct individual cat dose-
response curves. The cat’s AR was defined by the agonist concentra-
tion at which R, increased to 200% (ie, EClooR,) of the postsaline
challenge values or at which C,,, decreased to 65% of the postsaline
challenge values (ie, ECh,C,y,).6 This concentration was estimated
using linear extrapolation through the points bounding the actual
concentrations at which this effect was observed. The group means
and small-sample 95% CIS were determined for the ECzooRLand
EChjCdynconcentrations for the healthy cats. For the healthy cats,
the AR to methacholine while under thiamylal-induced anesthesia
(n = 7) was compared with the AR obtained during pentobarbital
anesthesia (n = 8) using a 2-tailed t - t e ~ tThe
. ~ ECIOORLand EChjCdyn
values of the affected cats were considered abnormal if they fell
below the lower 95% CI established for the group of healthy cats.
For all data, differences were considered significant if the test statis-
tic type-1 error was less than 0.05 (ie, P < .05).
Results
Clinical Evaluation
Each of the 15 healthy cats received a “combined bron-
chopulmonary disease score” of less than 10 with a mean
(?SD) score of 5.8 ? 2.3 points (Fig 1). This group included
13 Domestic Short Hair cats, 1 Domestic Long Hair cat, and
I Siamese cat. Eight cats were male and 7 were female. The
ages ranged from 1 to 15 years (mean ? SD, 4.2 ? 3.9
years). Of the 24 cats with bronchopulmonary disease, there
were 15 Domestic Short Hair cats, 4 Domestic Long Hair
cats, 3 Siamese cats, 1 Siamese-cross cat, and 1 Abyssinian
cat (Table 1). Sixteen (67%) were male and 8 (33%) were
female. Presenting signs are summarized in Fig 2. Eleven
of 24 (46%) cats with disease had signs for between 2 months
and 1 year, whereas 7 of 24 (29%) had signs for more than
1 year.
Five cats received combined scores between 12 and 22
points and were placed in the clinically mild disease group
(Fig 1). This group included the 2 cats obtained directly
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387
50
45
Radiology Score
40 0 Physical Exam Score
History Score
35
30
25
20
15
1o
0
Healthy Mild Moderate Severe
Fig 1. Histogram of the combined results of the clinical evalua-
tion, which resulted in a ”combined bronchopulmonary disease
score” (maximum theoretical score of 100). thereby allowing compar-
ison of the affected cats on the basis of relative disease severity.
from the OLAC facility. These cats did not have an owner-
defined history score, and they were assigned a history score
equivalent to the lowest history score of any of the affected
cats. Twelve cats scored between 22 and 32 points and were
placed in the moderately affected group. This group included
1 cat (cat 6) that “whistled and wheezed” during sleep and
had had acute respiratory distress 3 years earlier. There were
2 radiolucent areas in the caudal lung lobes suggestive of
emphysematous bullae on radiographic evaluation of this
cat. Bronchoscopy was performed to assess gross airway
changes, but unfortunately pneumothorax developed during
the procedure. Air leakage was controlled by placement of
a chest tube until the reinflated lung sealed. The cat has had
no further dyspneic episodes but continues to “whistle”
during sleep. Finally, 7 cats scored between 32 and 46 points.
These subjects were considered to have severe disease (Fig
I). This group included the cat with the highest history score
(cat 19), highest physical examination score (cat 23), and
highest radiographic score (cat 21). Cat 23 had coughed for
more than 8 years and more recently exhibited intermittent
wheezing and dyspnea. There were coarse crackles, wheezes,
and decreased chest compressibility on physical examina-
tion, whereas diffuse bronchial thickening and unstructured
interstitial changes were present on thoracic radiographs.
In 1 Siamese cat (cat 21), tracheal palpation easily elicited
coughing after which severe crackles, wheezes, and aug-
mented bronchial sounds were auscultated. The chest wall
was palpably noncompliant. A hyperinflated, barrel-shaped
thorax with generalized, severe bronchial patterns, interstitial
disease, collapse of the left cranial lung lobe, and changes
suggestive pf bullous emphysema were observed on thoracic
radiographs.
At the time of evaluation, the known ages of the affected
cats ranged from 4 months to 13 years (mean 2 SD, 4.9 ?
3.3 years). There were no marked differences in age among
the cats with clinically mild (5.3 ? 3.1 years), moderate (4.6
2 2.1 years), or severe disease (5.1 ? 4.7 years).
Grouped by clinical severity, data on the CBCs are pre-
sented in Table 2. Relative to the healthy cats, moderately
affected cats had greater numbers of circulating neutrophils,
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388 DYE ET AL

Table 1. Signalment and Baseline Pulmonary Function Measurements of 24 Cats With Bronchopulmonary Disease
Primary Disease
Cat Breed Age (Y) Complaints* Durationt Severity RL Cdyn
1 DLH 2 (est) NA NA Mild 16.6 16.4
2 DSH 8 3 5 Mild 24.0 20.0
3 DS H 4 1 5 Severe 24.8 25.0
4 DSH 7 1, 3 4 Moderate 27.0 10.0
5 DSH 1.2 1. 5 4 Moderate 30.8 18.4
6 DSH 5 2 (3?) 5 Moderate 32.1 18.4
7 Siamese 9 1 4 Moderate 32.9 18.2
8 DSH 2 1 4 Mild 34.1 15.3
9 DLH 1.2 1 4 Moderate 35.4 6.0
10 Siamese-X 5 1, 5 4 Moderate 39.0 20.8
11 Abyssinian 3 1 5 Moderate 39.8 18.5
12 DSH 5 1, 3. 4 4 Moderate 42.4 27.3
13 DSH 6 4 4 Moderate 43.7 29.7
14 DSH 6 1 2 Mild 45.3 10.8
15 DSH 3 1 2 Moderate 60.7 13.4
16 DSH 0.3 1. 3, 4 3 Severe 66.4 6.3
17 DSH 5 1. 5 4 Moderate 69.3 22.0
18 DLH 2 (est) NA NA Mild 71.4 11.2
19 DSH 1 1. 5 4 Severe 76.2 13.5
20 DSH 5 4 2 Moderate 84.7 9.2
21 Siamese 7 1, 4 5 Severe 90.8 19.4
22 Siamese 13 1 5 Severe 100.1 11.0
23 DSH 9 1. 3. 4 5 Severe 153.0 5.0
24 DLH 2 1 4 Severe 229.0 7.0
Abbreviations: DSH, Domestic Short Hair; DLH, Domestic Long Hair; est, estimate; NA, not available; RL, lung resistance = c m H201Lk; Cdyn,
dynamic lung compliance = mUcm H,O.
* 1, coughing; 2, abnormal or noisy breathing; 3, wheezing; 4, difficulty breathing; 5, sneezing.
t 1, <1 wk; 2, >1 wk but <1 mo; 3, >1 mo but <2 mo; 4, >2 mo but <1 y; 5, >I y.

whereas severely affected cats had greater numbers of circu-
lating neutrophils and monocytes. Peripheral eosinophilia
(defined as > 1,500 eosinophils/pL)R,qwas absent in control
cats, but was present in 1 of 5 cats (20%) with mild disease,
in 3 of 12 cats (25%) with moderate disease, and in 4 of 7
cats (57%) with severe disease. Specifically, cat 18 had an
eosinophil count of 1,540 cells/pL, whereas moderately dis-
eased cats 7, 10, and 20 had eosinophil counts of 1,550
cells/pL, 1,740 cells/pL, and 6,450 cells/pL, respectively.
Severely affected cats 16, 22, 23, and 24 had eosinophil
counts of 1,920 cells/pL, 1,520 cells/pL, 2,070 cells/pL, and
2,000 cells/pL, respectively. Neither clinical nor biochemi-
cal evidence of renal or hepatic disease were present in any
subject. Total serum protein concentrations of >8.0 g/dL
were present in 4 of the affected cats, only 2 of which (cats
coughing
Signs of Obstruction
wheezing
difficulty breathing
noisy or abnormal
breathing patterns
Fig 2. Presenting signs of the cats with bronchopulmonary
disease.
21 and 22) had hyperglobulinemia (>4.5 g/dL).'" Three of
the clinically healthy cats were shedding ascarid ova, 2 of
which (cats K and 0) had peripheral eosinophil counts be-
tween 1,200 and 1,500 cells/pL. Ascarid and hookworm ova
were identified in only 1 affected cat (cat 16). This cat was
presented to the emergency room at 4 months of age with a
2-month history of coughing and wheezing that had pro-
gressed to severe dyspnea. Generalized interstitial and bron-
chial patterns were present on thoracic radiographs. After
anthelminthic and short-term prednisolone therapy for pre-
sumed parasitic-induced pneumonitis, the cat was clinically
healthy.
Occult heartworm testing was performed in 13 of 15 of
the healthy cats and 21 of 24 of the affected cats. All test
results were negative including 1 cat (cat 13) that had a
positive titer (both antibody- and antigen-based) 1 year ear-
lier. On presentation at that time, the cat was dyspneic and
cyanotic. Radiographs had revealed diffuse bronchial thick-
ening but no evidence of vascular (ie, heartworm-induced)
disease. Eosinophils were present in airway cytological spec-
imens. Serum globulin concentration was increased (5.4 gl
dL), but peripheral eosinophilia was absent. Bronchodilators
and prednisolone were administered for nearly 1 year, and
except for occasional coughing, no other complications de-
veloped. The cat was tapered off medication and I month
later was evaluated as part of this study. On our evaluation,
globulin concentrations were normal, but crackles and
wheezes were auscultated and eosinophils were still present

BRONCHOPULMONARY DISEASE IN THE CAT
Table 2. The Group Mean ( S E ) White Blood Cell Counts and Counts of Individual Affected
Cats With Leukocytosis
Total WBC
Disease Severity or Cat ID n (cells/pL)
Healthy 15 9,000 (750)
Mild 5 8,400 (1,260)
Moderate 12 12,250 (2,100)
Severe 7 15,050 (2,990)*
5 24,400
16 31,900
20 28,500
Abbreviation: WBC, white blood cells.
* Significantly different than the group of healthy cats.
t Exclusive of the 2 control cats shedding ascarid ova.
in the bronchial wash sample. Radiographically, the heart
and pulmonary vessels remained normal, but a generalized
bronchial pattern persisted.
Six cats had signs suggestive of an upper respiratory tract
infection (URTI). However, attempts to isolate viral particles
from tonsilar swabs had negative results in all 6 cats. Cats
with presumed URTI included cat 10, a Siamese-cross with
sneezing and nasal discharge that decreased with antibiotic
therapy. The cat entered this study after 4 months of contin-
ued sneezing and coughing. The nasal discharge was no
longer apparent, but severe bronchial thickening and an inter-
stitial pattern were observed on thoracic radiographs. The
cat improved clinically after treatment with prednisolone for
2 months, but radiographic abnormalities persisted. Shortly
thereafter, another cat in the same household (cat 8) began
to cough, primarily after exercise. A generalized mild-to-
moderate bronchial pattern was present on thoracic radio-
graphs. Cat 19 was obtained at 6 months of age from a
shelter and, despite prior vaccinations, developed coughing,
sneezing, and purulent nasal discharge. The cat had under-
gone intermittent antibiotic treatment for URTI for 8 months
prior to referral. On our evaluation, nasal discharge was still
present; radiographically there was a mild bronchial pattern.
Three months after obtaining this cat, an older cat in the
household (cat 17) also began to cough and sneeze; the
coughing was partially responsive to prednisolone. Radio-
graphically, cat 17 had a moderately severe, generalized
bronchointerstitial pattern with collapse of the right middle
lung lobe.
Tracheobronchial Bacterial Cultures
Results of 10 of 13 (77%) quantitative cultures performed
on the healthy cats were positive. Of these, 5 of 10 (50%)
yielded 100 to 300 colony-forming units per milliliter ( c f d
mL) and 5 of 10 (50%) yielded >2,000 cfu/mL (Table 3).
One of the isolates was identified as belonging to the Centers
for Disease Control biogroup Va- 1. Multiple isolates were
obtained from several cats. Originally, Acinetobacter cal-
coaceticus and Corynebacterium sp. were isolated from cat
E. One week later, without treatment, y-Staphylococcus sp.,
a-Streptococcus sp., and Pasteurella sp. were isolated.
Microbial isolates were obtained from 10 of 24 (42%)
cats with bronchopulmonary disease (Table 4). Of the 10
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389
~ ~~
Neutrophils Lymphocytes Eosinophils Monocytes
(cells/pL) (cells/pL) (cells/pL) (cells/pL)
4,120 (460) 3,980 (600) 600 (110) 195 (30)
490 ( 9 0 ) t
4,410 (620) 3,030 (700) 560 (280) 240 (60)
7,030 (1150)* 3,430 (700) 1,220 (500) 330 (70)
10,220 (2080)" 2,900 (800) 1,470 (220) 460 (120)*
14,400 8,540 1,220 240
21,700 7,340 1,920 960
11,350 7,220 6,450 260
positive cultures, only 4 yielded > 100 cfu/mL, including
Pasteurella sp., Moraxella sp., Bordetella sp., Alcaligenes
denitrijicans, and Pseudomonas pseudoalcaligenes (also
known as Pseudomonas pickettii).
Tracheobronchial Cytology
Brushing and washing cytology data for individual healthy
and affected cats are presented in Tables 3 and 4, respec-
tively. Cells comprising 8% of the total or fewer were not
tabulated. These cells included occasional neutrophils, lym-
phocytes, mast cells, eosinophils, plasma cells, or squamous
cells. None of the samples from healthy cats had greater
than 4% eosinophils. Interestingly, the wash from cat C (the
only control cat with smokers in the household) contained
macrophages with darkly pigmented, intracytoplasmic parti-
cles, similar to those observed in macrophages in the sputum
of cigarette smokers. In affected cats, there was considerable
variability in the types of inflammatory cells present and
wash samples frequently contained a greater percentage of
neutrophils and eosinophils than did the corresponding
brushing sample. There was no apparent correlation between
the presence of inflammatory cells in the wash sample and
the presence or absence of a positive bronchial culture, nor
was there a correlation between the percentage of eosinophils
in the wash sample and in the peripheral blood. Affected
cats had markedly lower percentages of epithelial cells in
their wash samples, owing to an increase in the combined
percentage of eosinophils and neutrophils (Fig 3A). Further-
more, ANOVA with Fisher's PLSD assessment indicated
that, relative to the healthy cats, severely affected cats had
significantly higher percentages of eosinophils, neutrophils,
and combined eosinophils and neutrophils, whereas moder-
ately affected cats had a greater percentage of eosinophils
and neutrophils (Fig 3B).
Baseline Pulmonary Function Testing
After induction of anesthesia, cats typically experienced
a brief period of apnea before resuming a stable breathing
pattern. During data acquisition, respiratory rates ranged
from 9 to 30 respirations per minute (mean, 17 respirations
per minute). All cats recovered rapidly from the baseline
testing procedure and were released later the same day.
Results of baseline pulmonary function testing in the 15
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390 DYE ET AL

Table 3. Baseline Pulmonary Function Measurements and Clinicopathologic Results in 15 Healthy Cats
Cat RL Cdyn Culture Identification Culture (cfu/rnL) Brushing Cytology* Washing Cytology”

A 22.0 32.0 Staphylococcus sp. 100 95% Epi 63% Epi, 37% PMN
B 22.0 24.7 Flavobacteriurn 13,000 89% Epi NA
a-Streptococcus sp. 10,000
C 23.6 35.7 Staphylococcus 100 80% Epi, 20% M 0 84% M0, 16% Epi
D 23.7 25.5 Bordetella bronchiseptica 50,000 70% Epi, 17% 57% Epi, 23% M0, 12%
Enterobacfer agglomerans 1,200 Unidentified, 9% M 0 PMN
E 24.3 13.4 Acinetobacter calcoaceticus 30,000 92% Epi No cells observed
Corynebacteriurn sp. 1,000
F 24.8 16.7 CDC biogroup VA-1 30,000 99% Epi 70% unidentified, 30% M 0
G 25.8 15.2 Bordetella bronchiseptica 100,000 44% PMN. 22% M0. 77% €pi, 11% unidentified,
21% Epi 9% PMN
H 26.8 24.3 NG - 96% Epi 98% Epi
I 29.0 16.3 Klebsiella ozaenae 200 98% Epi 50% PMN, 38% M 0
J 29.5 20.4 NA - 74% Epi, 25% M 0 65% Epi, 34% M 0
K 30.5 16.5 Fastidious Gram-negative rod 100 100% Epi 100% Epi
L 33.3 10.5 Pasteurella multocida 300 85% Epi, 9% PMN NA
M 36.0 19.0 NA - NA NA
N 39.0 15.6 NG - 88% Epi 54% Epi, 42% M 0
0 43.0 11.0 NG - 91% EDi NA

Mean 28.9 19.8

Lower 95% CI 25.3 15.7
Upper 95% CI 32.4 23.9

Abbreviations: RL,lung resistance = crn H,O/Us; Cdyn, dynamic lung compliance = mUcm H,O;NG, no growth; NA, not available; Epi, epithelial
cells; PMN, neutrophils; M0, macrophages.
* Only cell types present at 2 9 % are listed

healthy cats are presented in Table 3. Including the endotra-
cheal tube, the mean (2SD) RL in these cats was 28.9 (56.2)
cm H,O/L/s with an overall CV of 22%. Therefore, the RL
small-sample 9.5% CI was 25.3 to 32.4 cm H,O/L/s. The
mean Cdynwas 19.8 (k7.4) mL/cm H 2 0 with a somewhat
larger CV, 37%. Therefore, the 95% CI for Cdynranged
from 15.7 to 23.9 mL/cm H20. To account for the greater
variability in the Cdynmeasurements in healthy cats, attempts
were made to correlate Cdynwith another parameter. There
was no apparent relationship between baseline function mea-
surements and weight or age. However, as shown in Fig 4,
the strongest correlation ( Y = .75, P = ,005) resulted from
comparison of each healthy cat’s Cdynmeasurement with that
of its thoracic girth, as measured at the level of the last
sternebra.
The results of baseline testing in the 24 affected cats are
presented in Table 1. The mean RL (ZSD) of the mild, mod-
erate, and severe groups were 38.3 ( 2 2 1 3 , 44.8 (t17.7),
and 105.2 (266.9) cm H20/L/s, respectively (Fig 5 ) with 3
of 5 (60%) of the mildly affected, 9 of 12 (75%) of the
moderately affected, and 6 of 7 (86%) of the severely af-
fected cats having baseline RL measurements above the upper
95% CI established in the healthy cats. The mean Cdyn( t S D )
of the mild, moderate, and severe groups were 14.7 (k3.8),
17.7 (t6.9), and 13.0 (k7.9) mL/cm H20, respectively (Fig
S ) , with 3 of 5 (60%) of the mildly affected, 4 of 12 (33%)
of the moderately affected, and 6 of 7 (86%) of the severely
affected cats having baseline Cdyn measurements below the
lower 95% CI established for the healthy cats. Additionally,
the baseline Cdyn of 2 moderately affected and 1 severely
affected cats exceeded the upper 95% CI.
In affected cats, correlations between individual RL and
Cdynmeasurements and various clinical parameters were ana-
lyzed. There were weak correlations between RL versus the
combined disease score ( r = .48, P = .017), the radiographic
bronchial pattern score ( r = .57, P = .004), and the physical
examination score ( r = .59, P = ,002). No correlations were
apparent between Cdynand these clinical parameters. In gen-
eral, the more severe the disease was clinically, the higher
the RLmeasurements were and the smaller the corresponding
Cdynmeasurements were, but there was considerable variabil-
ity within each group.
Acute Response to a Bronchodilator
After terbutaline administration, RL measurements typi-
cally decreased, whereas the corresponding Cdynmeasure-
ments increased, as did heart rate. Peak responses occurred
within the first few minutes. The duration of terbutaline’s
bronchodilatory effect was not determined, in an attempt to
avoid prolonged anesthesia. In some of the cats, RL measure-
ments decreased initially and then began to increase within
10 minutes of the injection. The average changes in RL, Cdyn,
and heart rate are presented in Table 5 . Analysis of variance
indicated marked differences between groups for the maxi-
mal change (A) in R, after terbutaline administration (P
= ,016). Group differences in ACdy, were not significant.
Compared with healthy cats, moderately ( P = .04) and se-
verely ( P = .0l) affected cats had markedly greater decreases
in RL after terbutaline administration.
Cat 20 was 1 of a few cats evaluated during clinically
apparent respiratory distress. This cat was anesthetized
briefly for a bronchial wash, culture, and function testing,
and baseline RL was increased (84.7 cm H201L/s), whereas
C,,, was decreased (9.5 mL/cm H,O). Pending culture re-
 19391676, 1996, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.1996.tb02086.x by Nat Prov Indonesia, Wiley Online Library on [08/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BRONCHOPULMONARY DISEASE IN THE CAT 39 1

Table 4. Clinicopathologic Results of 24 Cats With Bronchopulmonary Disease

Periperal Fecal
Cat Eosinophilia Flotation Culture Identification Culture (cfu/mL) Brushing Cytology* Washing Cytology*

1 No Alcaligenes 100 44% Epi, 36% PMN, 54% Ma, 31% PMN,
20% M 0 15% Epi
2 No Staphylococcus 100 100% Epi 58% Ma, 40% Epi
3 No NG - 98% epi 70% M0, 25% Epi
4 No NG - 97% Epi 49% Eos, 40% M 0
5 No Pasteurella sp. 300
Moraxella sp. 1,600 81% Epi, 9% PMN 79% M0, 20% PMN
Borderella bronchiseptica 10,000
6 No Bacillus sp. 100 100% Epi 93% M a
7 Yes Alcaligenes denitrificans 7,200 NA 59% PMN, 30% EOS
8 No Corynebacterium sp. 100 61% Epi, 37% M 0 66% PMN, 33% MO
9 No Corynebacteriurn sp. 500 94% Epi 73% Epi, 17% Eos,
Streptococcus sp. 100 10% M 0
10 Yes NG - 91% Epi 76% PMN, 14% M0,
9% Lymph
11 No NG - 94% Epi 77% Epi, 11%
unidentified, 9% PMN
12 No NG - 98% Epi 65% Epi, 21% PMN,
12% M 0
13 No NG - 82% Epi, 17% M 0 58% EOS, 34% M 0
14 No Moraxefla sp. 100 53% Epi, 43% M 0 83% M0, 13% Epi
15 No NG - 64% PMN, 14% NA
unidentified, 10% Epi,
9% M 0
16 Yes NG - 40% Epi, 27% Eos, 62% Eos, 37% M 0
16% Lymph, 14% M 0
17 No NG - 100% Epi 73% Epi, 27% M 0
18 Yes NG - 95% Epi 49% PMN, 32% M0,
17% Epi
19 No NG - 57% Epi, 27% PMN, 48% PMN, 40% M0,
13% M 0 11% Lymph
20 Yes NG - NA 43% MO, 32% Eos,
15% PMN, 10% Epi
21 No Staphylococcus 100 96% Epi 86% PMN, 10% Epi
22 Yes NG - 83% Epi, 9% Eos 75% EOS,24% PMN
23 Yes NG - 50% Epi, 9% M 0 NA
24 Yes Pseudomonas Medium 39% PMN, 38% Epi, 88% PMN
pseudoalcaligenes growtht 11% M0, 11% EOS
Abbreviations: NA, not available; NG, no growth; Epi, epithelial cells; PMN, neutrophils; M0, macrophages; Eos, eosinophils; Lymph, lympho-
cytes; (-), negative.
* Only cell types present at 2 9 % are listed.
t Sample inadvertently plated nonqualitatively.

sults, the cat was treated with antibiotics and appeared to
improve. A BD response test was performed 2 days later
when culture results indicated no growth. At this time, RL
was normal (32.6 cm H,O/L/s), but Cdynwas still decreased
(13.7 mL/cmH20). After terbutaline administration, Cdyn in-
creased to 23.0 mL/cm H20, a value similar to those obtained
in the heathy cats. Thus, in addition to peripheral and airway
eosinophilia, cat 20 appeared to have reversible (either spon-
taneously or in response to treatment) airway obstruction.
Bronchoprovocation Testing
In these cats, the dose-response curves obtained in re-
sponse to aerosolized histamine were extremely variable,
regardless of whether thiamylal or pentobarbital anesthesia
was used. To avoid excessive bronchoconstriction, chal-
lenges were discontinued when Cdyn decreased to 65% of the
postsaline nebulization value. In healthy cats, however, this
histamine concentration did not significantly increase RL
(Table 6). During subsequent provocation testing, histamine
concentrations were increased beyond those required to de-
crease Cdynby 65%. When still higher histamine concentra-
tions were administered, Cdynoften increased rather than
continuing to decrease (Fig 6A). It was exceedingly difficult
to obtain consistent dose-response curves in the healthy cats
using aerosolized histamine, and ECzooRLconcentrations
could not be calculated. Although ECbSCdyn values are pre-
sented in Table 6, it is possible that initial decrements in
Cdynwould not have persisted if the challenges had been
continued beyond these concentrations (ie, through 10 mg/
mL). As a result of these inherent problems, only 1 of the
cats with bronchopulmonary disease (cat 15), underwent
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392 DYE ET AL

40 -
Healthy (n = 10)
Diseased (n = 22)
35 -

30 -
25 -

20 .

A " Epithelial
Cells
Macrophages Eosinophils Neuaophils Eosinophils +
Neutrophils
l5 t A

/
/A-

*
90
80
F Eosinophils T
20 25 30 35 40 45 50
2 70 Eosinophils + Neutrophils
Thoracic Girth (cm)
$ 60
Q Fig 4. Correlation of the thoracic girth of individual healthy cats
d 50
and their dynamic lung compliance measurements.
C
'2 40
3

$ 0
30

@ 20 were anesthetized with thiamylal sodium compared with

10
, n
" Healthy Mild Moderate
(n = 10) (n = 5) (n = 11)
Fig 3. (A) Percentage of cells present in washing samples (mean
-tSE) from healthy cats and cats with bronchopulmonary disease. (B)
Percentage of eosinophils and/or neutrophils present in the washing
samples, based on relative disease severity. 'Significantly different
from the group of healthy cats.
bronchoprovocation testing with histamine. However, in this
cat, the ECbSCdyn histamine concentration induced a doubling
of RL, when the cat was challenged under thiamylal- and
under pentobarbital-induced anesthesia (Table 6).
As an alternative, methacholine was used to evaluate the
pentobarbital. The airway responses of healthy cats under
the 2 anesthetic protocols were not pooled as a result of this
small but statistically marked difference. Instead, responses
Severe
(n=6) in affected cats were compared with those in the correspond-
ingly anesthetized healthy cats.
Aerosolized methacholine challenges also were performed
on 7 cats with bronchopulmonary disease. Based on the ease
of challenge completion with pentobarbital anesthesia in
healthy cats, most of the affected cats also were challenged
during pentobarbital anesthesia. For comparison, a few cats
were evaluated under both protocols. The resultant ECZOORL
and EChSCdyn concentrations in affected cats are compared

1
degree of AR in healthy cats. A typical dose-response curve
to aerosolized methacholine in a healthy cat (cat K) is pre-
sented in Fig 6B. When healthy cat I was anesthetized with
thiamylal sodium, we were unable to complete the challenge
because of the inability to suppress coughing that developed
after methacholine nebulization. During pentobarbital anes-
thesia, however, the challenge was completed without diffi-
culty. In general, we found that during pentobarbital-induced
anesthesia, the rate and depth of breathing remained more
constant, aerosol-induced coughing was less problematic,
and the challenges could be completed over a shorter time
necessitating fewer supplemental doses of the anesthetic
agent.
The arithmetic means of the ECZOORL and ECh5Cdyn metha-
choline concentrations for challenges performed in healthy
cats under thiamylal and pentobarbital anesthesia are pre- v

Severe
Healthy Mild Moderate
sented in Tables 7 and 8, respectively. There were no marked
differences in baseline or postsaline RLor Cdynmeasurements Fig 5. Results of baseline lung resistance (cm H,O/L/sl and dy-
or in ECZDORL between anesthetic protocols. However, the namic lung compliance (mL/cm H,O), mean ( 5 SEI of each group,
EC65Cdyn was significantly lower ( P = .03) when the cats based on relative disease severity.
 19391676, 1996, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.1996.tb02086.x by Nat Prov Indonesia, Wiley Online Library on [08/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
BRONCHOPULMONARY DISEASE IN THE CAT 393

Table 5. Acute Response (mean 5 standard error) After IV Administration of the Bronchodilator Terbutaline
Relative Disease Severity

Parameter Healthy Mild Moderate Severe Cat 18*

n 9 5 9 7
RL @ baseline 28.3 5 1.8 40.5 2 8.6 42.1 t- 4.7 105.9 2 25.2 108.7 120.0
ARL @ peak effect -3.4 2 1.7 -7.6 t- 4.0 -12.5 t- 4.7t -43.5 5 17.6t -50.9 -75.0
RL max. % change -10.9 ? 6.5 -15.6 t- 5.8 -26.0 2 6.2 -34.7 5 6.6 -46.8 -62.5
Cdvn@ baseline 20.1 t- 2.7 15.4 2 3.0 17.8 52.7 12.6 t- 2.8 7.8 6.5
AC, @ peak effect 6.1 t- 1.2 3.5 i- 1.4 5.3 5 2.4 5.2 ? 2.5 2.9 1.5
Cdynmax. % change 32.3 t- 5.8 22.0 t- 7.9 32.8 i- 12.6 45.1 t- 21.0 37.2 23.1
Baseline HR 180 t- 6 180 i- 15 170 t- 5 180 i- 7 160 180
HR @ peak effect 240 f 6 220 t- 15 230 2 8 230 -t 7 180 210
Abbreviations: n. number; RL, lung resistance = cm H20/L/s; @, at; A, Delta; Cdyn,dynamic lung compliance = mL/cm H20; HR, heart rate =
bpm.
* T w o additional bronchodilator response tests were performed in this cat over a 7-m0period.
t Significantly different than the group of healthy cats.

with those of the correspondingly anesthetized group of 220 1 I 220

healthy cats in Tables 7 and 8.
Using pentobarbital anesthesia, 6 of 7 (86%) affected cats
evaluated achieved a doubling of postsaline Rl measure-
ments at methacholine concentrations less than the lower 160 - 160
95% CI concentration calculated for healthy cats. Similarly,
the EChSCdyn concentrations were less than the lower 95%
- 140
CI in 5 of 7 (71%) affected cats evaluated. One cat (cat 1) - 120
was tested 3 times over a 4-month period and consistently - 100
was hyper-responsive, although the degree of AR varied. In - 80
cat 15, ECzooR, and EC6=,Cdyn values also were lower than
those of healthy cats, regardless of anesthetic protocol. In - 60
cat 18, relatively dilute methacholine concentrations induced
a marked absolute change in RL.Postsaline Rl was relatively
high in this cat, and higher concentrations of methacholine
were required to achieve a 200% increase in RL. Finally, cat d 1 10 100o
A Osal .1
14 did not exhibit increased responsiveness to aerosolized Aerosolized histamineconcentration (mg/mL)x 5 breaths.
methacholine, but when atropine was administered at the
end of the challenge, RL decreased to 31 cm HzO/L/s and
Cdvnincreased to 13 mL/cm HzO.
260
240 240
220 220
Table 6. Aerosolized Histamine Challenge 200 200
Concentrations (mg/mL) Required to Achieve the 180 180
EC,,,R, and EC65Cdyn in 8 Healthy Cats and 1 Cat
With Bronchopulmonary Disease
Thiamylal Pentobarbital

Cat ECZOORL ECsiCdyn ECzooRt EC&dyn

B > 10.0 0.4 >3.0 1.6
40 - -40
E
G
>3.0
>10.0
1.6
>10.0
>l.O
>3.0
0.7
>3.0 20
- 11
- 20
H >0.3 0.1 >3.0 1.4 O'.cY .. .....I . .. ...'.I . . . "'..' . . . ...- 0
Sal .1 1 10 1ou
I >l.O >1.0 >10.0 9.7
Aerosolized methacholine concentration (mg/mL)x 5 breaths.
K >3.0 2.4 >3.0 2.1
L >0.3 0.3 >1.0 0.5
6. (A) An example of a typical erratic dose-response curve
0 >3.0 2.8 >0.3 0.2
obtained during histamine bronchoprovocation testing in a healthy
15 2.4 2.0 0.3 0.2 cat (cat B). (B) An example of a typical dose-response curve obtained
during methacholine bronchoprovocation testing in a healthy cat (cat
Abbreviations: EC2&, effective histamine concentration (mg/mL) K). The ECzooRLin this methacholine challenge occurred at 7.1 m g l
required to double R;, ECBCCdyn,histamine concentration (mg/mL) re- mL and the EC,,C,. occurred at 9.3 mglmL. (RL, lung resistance =
quired to reduce Cdvnt o 65% of the postsaline measurement. cm HzO/L/s; Cdvn,dynamic lung compliance = mLlcm H,O)
 19391676, 1996, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.1996.tb02086.x by Nat Prov Indonesia, Wiley Online Library on [08/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
394 DYE ET AL

Table 7. Aerosolized Methacholine Challenge coughing may transport secretions from one area of the lung
Concentrations Required to Achieve the ECzooRL and to another or deeper into the periphery of the lung.'* Thus,
EChsCdyn in 7 Healthy Cats and 3 Cats With bacterial infections in human patients with severe airway
Bronchopulmonary Disease During Thiamylal obstructive disease can be difficult to manage." Some cats
Sodium-Induced Anesthesia with bronchopulmonary disease also may have alterations in
Group EC&dyn
their normal pulmonary defense mechanisms that may allow
for repeated or prolonged bacterial colonization of their air-
Healthy
ways. If so, bacterial involvement in affected cats would be
Mean ( i S E ) 6.5(21.8) 4.7 ( ~ 3 . 8 )
Lower 95% CI 2.0 2.2
a secondary complication of underlying bronchopulmonary
Upper 95% CI 10.9 7.3 disease and not a primary initiating event. This could explain
Mild Cat 1 <0.01* SO.Ol* the failure to resolve clinical signs in some affected cats
Moderate Cat 15 1.6* 1.2* (eg, cat 24), which had persistent coughing despite negative
Mild Cat 18 3.4 2.2 bronchial cultures after antibiotic therapy. On the other hand,
Abbreviations: ECZOORL, effective rnethacholine concentration (rng/ certain infectious organisms such as Mycoplusma pulmonis
rnL) required to double RL; ECB5Cdyn, rnethacholine concentration (mg/ have been shown experimentally to induce changes in the
rnL) required to reduce Cdynto 65% of the postsaline measurement. airway mucosa (eg, increased numbers of mucous-producing
* A value below the lower 95% CI for the group of healthy cats. cells). These changes may persist long after the inciting or-
ganisms have been effectively eliminated by antibiotic ther-
apy.14
Several of the cats in this study both sneezed and coughed.
Discussion Sneezing is an explosive reflex induced by stimulation of
Bronchopulmonary disease is a common but poorly under- irritant-type receptors in the nasopharyngeal area." In the
stood problem in cats.'-' Affected cats are thought to have cat, sneezing and nasal discharge most commonly are associ-
some degree of airway obstruction, but actual measurements ated with URTI caused by rhinotracheitis and calicivirus.
of lung function have not been reported previously. One Lower respiratory tract involvement in cats with viral infec-
purpose of the present study was to better document the tions may be missed clinically because upper respiratory
presence and degree of airway obstruction in cats with natu- tract signs are more marked and may predominate. The num-
rally occurring bronchopulmonary disease. Another goal was ber of cats in our study is small, but these results suggest
to assess the reversibility of airway obstruction if present, a temporal or causal relationship between respiratory viral
or alternatively, to assess the extent of AR present. infection or rhinitis and development of bronchopulmonary
In a retrospective study, Moise et al' reported that cats disease. Alternatively, infection may have exacerbated pre-
with bronchopulmonary disease were more likely to be Sia- viously occult lower respiratory tract disease. Failure to iso-
mese, female (67%), and between the ages of 2 and 8 years. late viral particles in these cats does not rule out viral infec-
In our study, 17% of the cats were Siamese or Siamese- tion because viral isolation is difficult when samples are
cross, similar to the 16% reported by Moise et al. In our collected late in the course of disease.16 More direct evidence
study, affected Siamese cats followed a more progressive
disease course. Of the 4 Siamese cats evaluated, 2 (cats 7
and 10) had moderately severe disease, and 2 (cats 21 and Table 8. Aerosolized Methacholine Challenge
22) were severely affected. Over a 3-year period, cat 21 Concentrations Required to Achieve the ECzOoRL and
had progressive worsening of clinical signs and radiographic ECLICdyn in 8 Healthy Cats and 7 Cats With
changes despite treatment with BDs and prednisolone. The Bronchopulmonary Disease During Pentobarbital
ages of the cats in our study were similar to those reported Sodium-Induced Anesthesia
by Moise et al,' but the predisposition toward female cats Group EC~OORL EC.&yn
was not found in our study, as 67% of affected cats were Healthy
male. Female cats in our study tended to be in the moderately Mean ( 2 SE) 9.1 2 1.8 9.1 2 1.4
to severely affected groups. Lower 95% CI 4.8 5.8
The clinical findings in affected cats included excessive Upper 95% CI 13.4 12.4
reflexes (ie, coughing, sneezing); physical evidence of air- Mild Cat 1 0.6* 0.7*
way secretions (ie, crackles), obstruction (ie, wheezing), and Mildt Cat 1 1.2* 1.2*
Severe Cat 3 3.5* 2.0*
increased tracheal sensitivity; radiographic evidence of bron-
Mild Cat 8 2.0* 6.3
chial and interstitial pulmonary disease; and cytological evi-
Moderate Cat 10 0.9* 0.14"
dence of airway inflammation or mucous secretions. In this Mild Cat 14 >10.0 >10.0
study, coughing, either alone or in combination with other Moderate Cat 15 2.2* 2.2'
signs, was the most common presenting complaint. The Mild Cat 18 1.8* 1 .o*
coughing may have been caused by bronchoconstriction, ex- ~ ~

Abbreviations: ECnooRL,effective methacholine concentration {rngi

cessive airway secretions, or tracheobronchial inflammation
and irritation." Normally, the cough reflex serves to propel
excess secretions out of the larger airways. In human patients
with chronic bronchitis or emphysema, the cough reflex is
of limited effectiveness in clearing secretions. Instead,
rnL) required to double RL; ECB5Cdyn,
rnethacholine concentration (mg/
rnL) required t o reduce Cdynto 65% of the postsaline measurement.
* A value that fell below the lower 95% CI for the group of healthy
cats.
t Challenge repeated 4 months after the first test.

BRONCHOPULMONARY DISEASE IN THE CAT
may arise from controlled experimental studies, such as that
by Killingsworth et all7 studying the effect of viral infection
on tracheal smooth muscle in cats.
Viral (parainfluenza virus, respiratory syncytial virus, in-
fluenza virus, and adenovirus) and mycoplasma infections
initiate bronchospasm and exacerbate asthmatic signs in both
children and human adults.’”24The mechanism of this rela-
tionship is not clearly defined. The underlying mechanisms
may not be agent-specific and may be mediated through
common pathways, such as development of airway epithelial
damage and inflammation.” Furthermore, childhood respira-
tory illness appears to be an important risk factor for devel-
opment of chronic airway obstruction in adults.26 Virus-in-
duced lower respiratory tract disease in children is associated
with the development of airway obstruction and increased
AR, and these changes may persist years beyond the original
infe~tion.*~.’~ Sinusitis is present in approximately 50% of
human patients with moderate to severe a ~ t h m a . ~Effective
’ study of Moise et al. Although not assessed in our study,
control of bronchospasm in patients with asthma may prove
difficult unless the sinusitis is treated c ~ n c u r r e n t l y .The
~~
mechanisms involved are poorly understood but most likely
involve a nasobronchial reflex pathway.28 This is supported
indirectly by findings in human as well as in some
laboratory animals.”
There are relatively few reports on normal flora in the
tracheobronchial tree of cats.”-34 Using protected catheter
brushes to obtain bronchial samples in 18 healthy cats, Pa-
drid et a134reported that 44% of aerobic cultures were posi-
tive. Isolates included Pasteurella sp., Pseudomonas sp.,
Staphylococcus sp., Streptococcus sp., Escherichia coli, and
Micrococcus sp., whereas attempts to isolate anaerobic bac-
teria or Mycoplasma sp. were unsuccessful. None of the
samples yielded >2,000 cfu/mL, and the investigators con-
cluded that, although the major bronchi in the cat were not
sterile, the bacterial numbers present usually were low. Simi-
lar results have been found in clinically healthy dogs, where
35 tracheal cultures obtained via guarded culture swabs, 36%
were p ~ s i t i v e . ~The
’ resident tracheal flora were similar to
the pharyngeal flora isolated simultaneously (including
streptococci, Pasteurella sp., staphylococci, and Klebsiella
pneumoniae), thereby suggesting that a potential source of
lower airway microbes is the recurrent aspiration of oral and
pharyngeal bacteria.3s
In our study, quantitative cultures were performed in an
effort to compare the quantity as well as the type of organ-
isms isolated in healthy and affected cats. Organisms isolated
in healthy cats included staphylococci, a common flora of
the skin and upper respiratory tracts of animals and human
beings; Pasteurella multocida, a common commensal organ-
ism of the oral cavity of cats; and Bordetella bronchiseptica,
considered to be part of the normal upper respiratory tract
flora in human beings and many animal species.36B bronchi-
septica also is the primary bacterium involved in infectious
canine tracheobronchitis, and both B bronchiseptica and
Pasteurella multocida have been isolated from laboratory
cats with pneumonia.32,’’
Many of the organisms isolated in the healthy cats were
organisms commonly found in the feline oropharyngeal area,
and one explanation for these findings would be oral contam-
ination of the sample during collection. However, it is more
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395
likely that the isolates were present in the tracheobronchial
tree itself because all cats were carefully intubated with a
sterile endotracheal tube and culture material was collected
with a protected catheter brush. We further hypothesize that
these isolates were the result of aspiration of oropharyngeal
secretions. The clinical significance of these isolates is un-
known, but their presence supports the finding that the bron-
chi of the cat are not always sterile. Therefore, the normal
flora (transient or resident organisms) of the feline lower
airways must also be considered when interpreting cultures
from cats with suspected bronchopulmonary disease.
Moise et a13 isolated bacteria in 12 of 49 (24%)cats with
bronchopulmonary disease, and the most frequent isolates
were Moraxella sp. and P multocida. In the present study,
10 of 24 (42%) affected cats had positive aerobic cultures,
of which only 3 yielded >2,000 cfu/mL. Additionally, Myco-
plasma sp. were isolated in 4 of 9 specimens cultured in the
Mycoplasma sp. have been isolated from the oral cavity of
normal cats.’7 The bacteria obtained in the study of Moise
et al’ may have originated from aspiration of oral secretions.
Many of the genera isolated from both healthy and af-
fected cats in our study (Acinetobacter, Alcaligenes, Borde-
tella, Flavobacterium, Moraxella, Pseudomonas), are Gram-
negative, nonfermentative bacilli. In human medicine, with
the exception of Pseudomonas aeruginosa, the nonferment-
ers generally are considered to be of low virulence, mostly
causing nosocomial infections in debilitated patients or in
patients receiving prolonged antibiotic or corticosteroid ther-
apy. Pseudomonas sp. are notorious for causing nosocomial
infections, particularly under moist conditions such as occur
when nebulizers or other respiratory equipment are used. In
veterinary medicine, Pseudomonas sp. also are considered
to be opportunistic agents and nosocomial infections are
common.36
We used a relatively simple method5to evaluate intralumi-
nal cytology of the tracheobronchial tree. No attempt was
made to measure the precise volume of wash material recov-
ered or to quantify the number of cells per milliliter present
in the cytological specimens. Therefore, we are unable to
compare absolute numbers of the various cell types present
in healthy versus affected cats. Based on the relative propor-
tions of cells collected, inflammatory cells (ie, eosinophils
and neutrophils) were increased in wash samples from mod-
erately and severely affected cats. Using a similar cytological
collection method, Moise et a15 also reported that bronchial
washes from healthy cats contained columnar epithelial cells,
small amounts of mucus, occasional macrophages, and rare
neutrophils, whereas washes containing eosinophils or in-
creased numbers of neutrophils were indicative of airway
inflammati~n.~ Other investigators, using bronchoalveolar la-
vage (BAL), reported that high numbers of eosinophils are
consistently present in samples from healthy cats.34 Com-
pared with specific pathogen-free cats, BAL fluid samples
from conventionally reared cats contained higher numbers
of eosinophils and ne~trophils.~’ In our study, the more se-
vere the cat’s disease appeared clinically, the more often the
cat had peripheral eosinophilia. However, cats with periph-
eral eosinophilia did not necessarily have a high percentage
of eosinophils in their washes. Thus, circulating eosinophilia

396
was not predictive of the type of bronchial inflammation
present in these cats, nor was this true in the cats described
by Moise et al.’ When guarded brushing samples are used
to obtain culture material, one also should obtain a separate
washing sample, because this may be more representative
of the types and numbers of intraluminal inflammatory cells
present. Further standardization of technique and interpreta-
tion of cytology samples from the conducting airways of the
cat is necessary. As reviewed re~ently,’~,~” this is a rapidly
developing diagnostic area in human as well as veterinary
medicine.
The R,. measurement is defined as the change in pressure
required for a given change in airflow at isovolume lung
conditions. As the diameter of the airway decreases, greater
pressure is necessary to achieve the same airflow. In the
respiratory system as a whole, all patent airways influence
the RL measurement; however, the “large” (or central) air-
ways appear to have the greatest influence. The RL measure-
ment is considered relatively insensitive to “small” (or pe-
ripheral) airway changes4’ In human beings, the “small”
airways are defined as being less than 2-mm internal diame-
ter, whereas in other species, this division is less well-de-
fined. Increases in RL generally indicate the presence of cen-
tral airway obstruction, with or without peripheral airway
obstruction. Airway obstruction may result from changes in
the airway lumen (eg, mucus, inflammatory debris), changes
in the wall (eg, thickening caused by submucosal edema and
inflammation, smooth muscle hypertrophy and constriction),
or changes in the tissues surrounding the airways (eg, em-
p h y ~ e m a ) . ~With
* distal obstruction, lung volumes may in-
crease because of air trapping, thereby decreasing RL as the
airways lengthen. Unless adjustments are made for increases
in lung volume, the sensitivity of the R,, measurement is
further reduced. Consequently, the finding of increased RL
cannot be used to differentiate the underlying pathological
abnormalities present, but rather is a reflection of airflow
resistance at the time the measurement was obtained.
Lung compliance serves as an index of overall lung “stiff-
ness,” representing the change in pressure required to induce
a given change in volume as calculated at 2 “isoflow” points
during a breath (eg, at the beginning and end of a breath).
Closure or constriction of “smaller” conducting airways (ie,
those larger than terminal bronchioles) appears to have a
major effect on this measurement, and lung compliance de-
creases during constriction of the “smaller” airways.43 Al-
ternatively, lung compliance may decrease after develop-
ment of infiltrative or fibrotic processes involving the
pulmonary p a r e n ~ h y m a . ~Conversely,
‘ in emphysema, in
which the elastic support structures of the pulmonary paren-
chyma are damaged or lost, Cdyntends to increase.44 Lung
resistance also tends to increase in emphysema because of
loss of radial traction on airways that normally helps to
maintain airway paten~y.~’
An ideal anesthetic agent for pulmonary function testing
would have minimal effects on respiratory drive and breath-
ing pattern (with no intrinsic bronchodilatory or constrictive
effects), it would maintain a constant depth of anesthesia
(with a uniform respiratory rate and depth), and it would
provide a smooth and rapid induction and recovery. Unfortu-
nately. no anesthetic agent meets all of these criteria. With
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DYE ET AL
the exception of ketamine, the commonly used sedative or
anesthetic agents (eg, xylazine, acepromazine, benzodiaze-
pine derivatives, barbiturates, opioid derivatives, halothane,
and isoflurane) all are associated with some degree of respi-
ratory d e p r e ~ s i o n Ketamine
.~~ would seem ideal because it
is used for short-term, minimally painful procedures in the
cat and is unique in its lack of cardiorespiratory depression.
When used as a single agent, however, ketamine alters the
pattern of breathing by prolonging inspiratory time and does
not abolish pharyngeal and laryngeal reflexes. Preservation
of these reflexes may lead to laryngospasm, bronchospasm,
or coughing secondary to oropharyngeal manipulation dur-
ing endotracheal tube placement,45 especially in cats with
pre-existing bronchopulmonary disease. Furthermore, be-
cause ketamine stimulates salivation, atropine typically is
administered as a premedicant. Atropine and related pre-
medicants could not be used in pulmonary function studies
because they interfere with airway muscarinic receptor func-
tion and disrupt vagally mediated bronchoconstriction. Con-
sequently, thiamylal sodium was chosen for baseline func-
tion testing in the cats of this study. In most cats, this
selection was adequate. In a few affected cats, apparently
because of increased tracheal sensitivity, it was difficult to
obtain functional measurements. At a light anesthetic plane,
some cats would cough as long as the endotracheal tube was
in place, but, if the plane of anesthesia was sufficiently deep
to eliminate the cough reflex, the respiratory rate became
overly depressed or apnea developed. Thus, the primary dis-
advantage of using thiamylal sodium was its inability to
block the coughing reflex in some cats with enhanced tra-
cheal sensitivity.
All cats were placed in sternal recumbency during func-
tion testing because this is thought to be most physiological
posture for pulmonary function testing in dogs. This body
position was not found to adversely affect peak flow rate or
lung volume measurements (eg, total lung capacity) in
dogs.46Fortunately, the size and shape of the thorax in cats
is relatively uniform, especially compared with other species
such as dogs and horses. Despite this, the CV of the Cdyn
measurement in healthy cats was relatively large, 37%. In
fact, 5 of 15 of the healthy cats’ Cdynmeasurements exceeded
the group-based 95% CI, whereas 4 of 15 were below the
95% CI. The relatively high percentage of healthy cats that
are “outliers” must be taken into account when interpreting
results in an individual animal. Thus, we attempted to corre-
late Cdynmeasurements to body size in the healthy cats. There
was no clear relationship between Cdynand body weight, nor
to allometric scaling of body weight to the 213 or 314 power.
There did appear to be a relationship between Cdyn and the
thoracic girth of the cat, and smaller cats (based on the
thoracic circumference) tended to have smaller Cdyn measure-
ments. In human beings, several pulmonary function mea-
surements correlate better with an individual’s height than
with weight.47
Most of the affected cats were not in obvious respiratory
distress when evaluated. Despite this, RL measurements were
significantly increased in many cats, consistent with obstruc-
tion of either the “larger” airways or severe, diffuse small
airway disease. Other cats had decreased Cdynmeasurements,
which could be due to either obstruction of the “smaller”

BRONCHOPULMONARY DISEASE IN THE CAT
airways or to parenchymal fibrotic or infiltrative processes.
In other cats, both RLand Cdyn measurements were abnormal,
consistent with disease processes involving the “large” and
“small” airways, with or without interstitial involvement.
A few of the cats had moderately increased Cdynmeasure-
ments in combination with slightly increased RL measure-
ments, consistent with the development of emphysematous
changes. Finally, several cats with vague signs (eg, cats 2
and 6) had baseline measurements that were only marginally
abnormal or were within the range of those in healthy cats.
The lack of strong correlations between the pulmonary
function measurements and individual clinical test results
(eg, radiographic scores) is further evidence that no single
diagnostic test can adequately evaluate an individual cat with
bronchopulmonary disease. This probably reflects a broad
spectrum of disease as well as the dynamic nature of airway
obstruction.
The acute changes in RL and Cdyn after terbutaline adminis-
tration presumably were due to smooth muscle relaxation
after stimulation of airway P,-adrenergic receptors. Even
healthy cats had RL decrements of approximately 10% and
Cdyn increments of over 30%. Post-BD Cdynvalues often were
above the upper range of the baseline Cdynmeasurements for
healthy cats. One explanation for this observation is that a
degree of smooth muscle tone normally may be present in
the “smaller” airways of healthy cats.
In an effort to obtain detectable pulmonary changes with-
out inducing marked cardiovascular effects, this “test” dose
of terbutaline was chosen because it was approximately 20-
fold less than that suggested for therapeutic use. Still, both
healthy and affected cats had consistent increases in heart
rate immediately after terbutaline administration. Without
direct blood pressure measurements, we were unable to de-
termine if these increases were caused by cardiac 0, -adrener-
gic receptor stimulation or a reflex response to blood pres-
sure changes secondary to peripheral vasodilatation.
After terbutaline administration, a few affected cats had
considerable improvement as their RL measurements re-
turned to “normal” or near-“normal” values. The nearly
complete response to a BD suggests that the majority of the
airway obstruction was caused by excessive smooth muscle
constriction. Such cats may have had reversible airway ob-
structive disease or “feline asthma.” It also is important to
recognize the waxing and waning nature of airway obstruc-
tion. Without a complete diagnostic evaluation, it would be
easy to associate rapid recovery of a cat, such as cat 20,
with antibiotic therapy. Realistically, however, the improve-
ment was most likely due to removal of the cat from the
environment that triggered respiratory decompensation and
to the supportive therapy provided until bronchoconstriction
spontaneously subsided. If other cats with clinical histories
of acute respiratory distress (cats 12 and 13) had been evalu-
ated during a period of distress, they too may have shown
more marked pulmonary functional improvement after terbu-
taline administration.
Although several of the affected cats had an initial decline
in R,, with or without improvements in Cdyn,R, remained
well above the post-BD range of healthy cats. Not surpris-
ingly, several of these cats had long-standing disease (eg,
cats 21, 22, and 23). In the cats with partial reversal of
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397
airway obstruction, other factors in addition to smooth mus-
cle constriction presumably were present (eg, intraluminal
secretions, inflammatory debris, mucosal or submucosal
edema, and inflammation). Finally, some of the cats had
negligible improvement. Such cats may have had chronic
bronchitis.
In humans, the degree of response to a BD is used diagnos-
tically. For example, after terbutaline inhalation, the forced
expiratory volume in 1 second (FEV,) increases an average
of 9% in healthy humans over a wide range of ages and
heights.4XTherefore, more than 15% improvement in FEV,
after inhalation of a BD is commonly used as supportive
evidence for the diagnosis of reversible airway obstructive
disease (eg, a ~ t h m a ) . ~In’ these cats, the significance of a
certain percentage change in RL or Cdynpost-BD measure-
ments is unknown because the FEV, measurement cannot
be compared directly with RL or Cdyn measurements. Further-
more, there are inherent problems in interpreting percentage
responses of parameters such as FEV,, because the more
severe the airway obstruction is initially, the smaller the
absolute change in FEV, needs to be to achieve a given
percentage change.4y Similarly, when the baseline Cdynis
very small (eg, cat l8), even a small absolute change after
BD administration is associated with a large percentage in-
crease. For this reason, in Table 5, both the absolute change
and percentage change in RL and Cdynwere presented. Al-
though we cannot definitively interpret the degree of bron-
chodilatory response, airway obstruction was at least par-
tially reversible in many cats. With regard to cats with less
apparent reversibility, it is important to note that human
patients with chronic airflow limitations often experience
symptomatic relief with chronic BD use, even if they failed
to show complete response during acute BD challenge.”
Seemingly, the acute response to inhaled P-agonists is not
always useful in predicting which patients are likely to bene-
fit from long-term BD therapy. In those human patients, and
presumably in these cats, a therapeutic BD trial of 2 to 4
weeks is indicated. Furthermore, it may be unwise to focus
solely on the reversibility of airway obstruction. Recent re-
ports suggest that over-reliance on P-agonist therapy (espe-
cially fenoterol) may be responsible in part for the current
increases in asthma-related morbidity and mortality in hu-
man The inflammatory component of broncho-
pulmonary disease in cats must not be ignored even if the
cat improves markedly during BD therapy.
Airway responsiveness is defined as the ease with which
airways narrow in response to a nonspecific (nonallergic or
nonsensitizing) stimulus.54~sy In humans, the degree of AR
commonly is assessed by monitoring a parameter of lung
function (eg, FEV, ), before and after inhalation of increasing
concentrations of histamine or methacholine. The challenge
is discontinued when a defined decrement occurs (eg, a 10%
to 20% decrease in FEV, from the postsaline measurement).
Inhalation of these same agonists causes airway constriction
in healthy subjects, but in asthmatic patients a considerably
smaller dose is needed to produce the same decrease in lung
function. Such patients have a heightened response to the
agonist and are said to have increased AR.5”,5yIncreased AR
is important not only as a key diagnostic feature of asthma,
but also because the degree of responsiveness appears to

398
correlate with the patient’s disease severity and therapy re-
quirements.55 Mildly increased AR often occurs in human
patients with chronic obstructive bronchitis,56 upper airway
disorders (eg, hay fever, chronic or allergic r h i n i t i ~ ) , ~and ~,’~
transiently after airway insults such as respiratory tract infec-
tions (especially viral infections),5x aeroallergen exposure,
or air pollutant exposure, including cigarette smoke.59,‘”The
mechanisms underlying development of increased AR are
complex” and beyond the scope of this report.
Other functional assessments must be used because FEV,
requires a maximal expiratory effort not possible in animal
studies. Commonly used end-points include predefined
increases in RL (eg, ECZOORL) or decreases in Cdyn(eg,
EC65Cdyn ). Similar to human challenge protocols, the agonist
delivered to these cats was administered during a defined
number of deep consecutive breaths. By monitoring the pres-
sure required to inflate the lungs, the depth of each breath
generated, and, presumably the dose of methacholine deliv-
ered were kept relatively constant. As long as the anesthetic
depth was adequate, the cats did not resist active inflation
of their lungs, even though they had not received neuromus-
cular blocking drugs. In experimental animal studies, sub-
jects often are chemically paralyzed and ventilated during
both aerosol delivery and acquisition of pulmonary function
measurements to achieve more defined control over the depth
and rate of respiration.62-” In our study of client-owned cats
with pre-existing pulmonary disease, we preferred to avoid
muscle paralysis if possible. In doing so, we avoided the
difficulty of weaning cats from controlled ventilation. Fur-
thermore, because many of the paralytic agents (eg, succinyl-
~ h o l i n e , ”atracurium,66
~ and h e ~ a r n e t h o n i u m ~have
~ ) been
shown to modulate airway responsiveness, their avoidance
was considered an additional benefit. By relying on sponta-
neous respiration in our cats while they were under general
anesthesia, inherent variability in tidal volumes and respira-
tory frequency occurred, contributing additional variability
in pulmonary function measurements.
Most experimental studies of histamine challenge in the
cat have used the IV route of admini~tration.~’-~” The dose-
response curves obtained in our cats also varied consider-
ably. Histamine administration in the cat may induce several
competing effects“-70; it can stimulate irritant receptors
within the “central” airways and induce bronchoconstriction
via a vagal reflex, or stimulate H, receptors in the “central”
and “peripheral” airways to induce bronchoconstriction. Al-
ternatively, histamine can induce catecholamine release from
the adrenal glands resulting in bronchodilation seconday to
,B2-adrenergic receptor stimulation. The erratic results ob-
served in this study suggest that aerosolized histamine ad-
ministration also was associated with 1 or more of these
competing effects. Therefore, aerosolized histamine does not
appear to be a reliable agonist for bronchoprovocation testing
in the cat.
Fortunately, bronchoprovocation testing with aerosolized
methacholine resulted in relatively consistent dose-response
curves in healthy cats. For this group of healthy cats, we
were able to determine a range of concentrations required
to induce airway constriction. Experimental studies suggest
that response to aerosolized methacholine in the cat is not
simply due to airway smooth muscle M,-receptor stimula-
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DYE ET AL
tion but rather to complex interactions among the adrenergic,
cholinergic, and nonadrenergic-noncholinergic inhibitory
(INANC) systems that regulate airways in cats.h3The iNANC
system is the predominant pathway by which airway smooth
muscle relaxation is induced in the cat,7’ whereas the dog
appears to lack this Based on in vitro studies of
airway smooth muscle, the iNANC system also is the only
demonstrable inhibitory system present in human airways.73
Some cats with bronchopulmonary disease experience
acute decompensation after exposure to dust or unusual
scents. This suggests that such cats also have increased AR.
In our study, several owners associated changes in the cat’s
environment with exacerbation of the cat’s clinical signs
including use of scented hair sprays, changing the brand of
litter to a clay-based product, changing the brand of litter to
a dustier type, and using a spice-scented air freshener near
the litter box (data not shown). In addition, 2 of the affected
cats had cigarette smokers in the household. In light of this
historical evidence, it is interesting that the majority (6 of
7, 86%) of the affected cats evaluated herein appeared to
have some degree of increased AR compared with the group
of healthy cats. During one of the methacholine challenges
in cat 1, inhalation of even the lowest methacholine concen-
tration (0.01 mg/mL) induced significant bronchoconstric-
tion. This concentration was 200-fold less than the lower
95% CI concentration of the healthy cats. In the 2 other
challenges in cat 1, the degree of responsiveness was only
somewhat increased, not unlike that associated with chronic
bronchitis56 or respiratory tract infections58 in human pa-
tients.
Cat 14 failed to show increased responsiveness to aerosol-
ized methacholine and also failed to show immediate im-
provement after BD administration. When this cat was given
atropine at the conclusion of the methacholine challenge, RL
decreased to near “normal” and Cdynimproved somewhat.
This was more improvement than the cat had in response to
terbutaline. It may be relevant that in human patients with
chronic bronchitis and emphysema, anticholinergic, antimus-
cainic drugs often are associated with more potent bron-
chodilatory effects than are ,&-adrenergic agents.74
Based on these results, airway obstruction was present in
many of the cats with bronchopulmonary disease, the degree
and reversibility of which varied from subject to subject. In
some cats, on an acute basis, airway obstruction was nearly
completely reversible. However, in most it was only partially
reversible, at least during the narrow time frame in which we
were able to monitor the cats after terbutaline administration.
Additional beneficial effects may be possible with longer
term therapy with terbutaline or other BDs. The functional
changes demonstrated in our study suggest that all cats with
bronchopulmQnary disease are not alike. It is hoped that,
with future study, bronchopulmonary disease in the cat will
be better understood, reflecting accurately prognosis and
ideal treatment strategy. The ability to objectively measure
pulmonary function will be essential, both as a diagnostic
tool and as a means of assessing response to therapy.
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