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Veterinary Internal Medicne - 2023 - Gareis - Correlation of Clinical and Radiographic Variables in Cats With Lower Airway

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Received: 3 February 2023 Accepted: 8 September 2023

DOI: 10.1111/jvim.16874

STANDARD ARTICLE

Correlation of clinical and radiographic variables in cats


with lower airway disease

Hannah Gareis 1 | Lina Hörner-Schmid 1 | Yury Zablotski 1 | Jelena Palic 2 |


Silke Hecht 3 | Bianka Schulz 1

1
Clinic of Small Animal Medicine, Ludwig
Maximilian University of Munich, Abstract
Munich, Germany
Background: Feline lower airway disease (FLAD) is frequently associated with
2
Division of IDEXX Laboratories, Vet Med
Labor GmbH, Kornwestheim, Germany
radiographic abnormalities.
3
College of Veterinary Medicine, University of Objectives: To evaluate whether radiographic changes in cats with naturally occurring
Tennessee, Knoxville, Tennessee, USA FLAD improve with treatment and if radiographic changes correlate with clinical signs.
Correspondence Animals: Twenty-four client-owned cats newly diagnosed with FLAD, based on medi-
Hannah Gareis, Clinic of Small Animal
cal history, typical clinical signs, radiographic findings, and examination of bronchoal-
Medicine, Ludwig Maximilian University of
Munich, Veterinaerstrasse 13, 80539 Munich, veolar lavage fluid, were included in the prospective study.
Germany.
Methods: At 2 examination time points (days 0 and 60), an owner questionnaire, clin-
Email: h.gareis@medizinische-kleintierklinik.de
ical examination, and thoracic radiography were carried out. Information from the
questionnaire and clinical examination were evaluated on the basis of a 12-point clin-
ical score. Radiographs were assessed using a 10-point radiographic score. Individual
treatment was given to all cats over the study period, based on severity of the dis-
ease and compliance of the cat. Clinical and radiographic scores were compared sta-
tistically for both examination time points and evaluated for correlation.
Results: All cats showed radiographic abnormalities at initial presentation. In addition
to significant improvement in clinical variables, the total radiographic score improved
significantly (P = .01) during the study period, with significant improvement in the
severity of bronchial (P = .01) and interstitial lung pattern (P = .04). Improvement of
the clinical and radiographic score was not correlated.
Conclusion and Clinical Importance: In addition to clinical signs, repeated radio-
graphic examination can be used as a diagnostic tool to evaluate treatment response
in cats with FLAD.

KEYWORDS
bronchoalveolar lavage, chronic bronchial disease, chronic bronchitis, feline asthma, radiography

1 | INTRODUCTION

Feline asthma (FA) and feline chronic bronchitis (CB) are collectively
Abbreviations: BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; CB, chronic
known as feline lower airway disease (FLAD) and cause clinical signs,
bronchitis; FA, feline asthma; FLAD, feline lower airway disease; IQR, interquartile range;
LMU, Ludwig Maximilian University. ranging from chronic cough and expiratory wheeze to episodes of

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for commercial purposes.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.

J Vet Intern Med. 2023;37:2443–2452. wileyonlinelibrary.com/journal/jvim 2443


19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
2444 GAREIS ET AL.

respiratory distress.1,2 The consequences of chronic airway inflamma- showing typical clinical signs of FLAD, were considered for inclusion
tion in FLAD are epithelial edema associated with infiltration of in the study. Enrollment was possible if the pet owner agreed to par-
inflammatory cells, hypersecretion of the goblet cells, and hypertro- ticipate, the cat was stable enough for diagnostic evaluation, and the
phy of the mucosa and submucosal glands and, additionally in FA, cat had not received antibiotics within 14 days before presentation.
bronchoconstriction caused by hyperreactivity of bronchial smooth Cats with bacterial growth or positive Mycoplasma spp. PCR in
muscle.3-5 In the long term, without control of inflammation, irrevers- bronchoalveolar fluid (BALF) was retrospectively excluded from the
ible pathological remodeling processes occur in the airways, also study. Patients were enrolled as a part of a previously published
known as airway remodeling.3,5,6 These changes result in airway substudy.17
3,7
obstruction, which leads to clinicopathological findings of FLAD.
The most common radiographic finding described in cats with FLAD is
an enhanced bronchial pattern caused by thickening of the bronchial 2.2 | Study sample
walls and increased mucus accumulation in small airways.3,5-9 In addi-
tion, interstitial or alveolar patterns, hyperinflation of the lung field, Twenty-four cats, diagnosed with FLAD on the basis of medical his-
and lobar atelectasis also have been described in affected cats.1,7,9-11 tory, clinical signs, and BALF examination findings, were included in
Radiographic signs suggestive of pulmonary hyperinflation include the study.
increased lung transparency and caudal flattening of the dia-
phragm.3,5,6,8,10 The right middle lung lobe is most commonly affected
by atelectasis as a consequence of mucus accumulation because of its 2.3 | Study design
dorsoventral orientation within the bronchial tree, and exposure to
the effects of gravity.1,3 All cats were presented at 2 examination time points (days 0 and 60).
Standard treatment of cats with FLAD consists of glucocorticoids, During the initial presentation on day 0, the cat's medical history was
sometimes with the addition of bronchodilators. The aim of treatment obtained using a standardized owner questionnaire modified from a
is to suppress airway inflammation and thereby eliminate the clinico- prior study,18 and a thorough clinical examination was performed.
3,5,6,12-14
pathological findings. Previous studies that investigated Each cat was assigned a previously published 12-point clinical score,19
radiographic findings in cats treated for FLAD showed controversial based on information derived from the owner questionnaire and clini-
results.15,16 One study found improvement of radiographic changes in cal examination findings. In cats with access to the outdoors, a Baer-
research cats with mild CB after administration of inhaled fluticasone mann fecal examination was performed to exclude lungworm
for 2 weeks.16 In contrast, a randomized study investigating radio- infection. Radiographs of the thorax were taken of each cat using
graphic findings in 9 cats with naturally occurring FLAD treated with 2 views and evaluated using a previously published 10-point radio-
systemic glucocorticoids for 7 days, followed by either inhaled flutica- graphic score.20 Bronchoalveolar fluid was obtained according to a
sone or systemic glucocorticoids, showed no improvement in radio- previously described protocol17 as a part of the initial assessment on
15
graphic variables after 8 weeks of treatment in either group. day 0. Bronchoalveolar lavage (BAL) was performed blindly in 23/24
Our aim was to investigate whether radiographic variables correlate cats and under endoscopy in 1/24 cats, endoscopy being indicated
with clinical signs as assessed using a standardized clinical score in cats because this cat showed focal alveolar infiltration radiographically.
with naturally occurring FLAD, and whether radiographic abnormalities The same board-certified clinical pathologist (JP) performed the cyto-
improve with individualized treatment. We hypothesized that radio- logical examination of all samples. The type of inflammation was clas-
graphic variables would improve with appropriate treatment to control sified according to the predominant cell types present: eosinophilic
the underlying airway inflammation in cats with FLAD, and that radio- inflammation (≥17% eosinophils, <7% neutrophils), neutrophilic
graphic improvement would correlate with clinical signs. inflammation (≥7% neutrophils, <17% eosinophils), and mixed inflam-
mation (≥7% neutrophils and ≥17% eosinophils).21 Aliquots of BALF
were sent to the LMU Institute for Infectious Diseases and Zoonoses
2 | MATERIALS AND METHODS for aerobic bacteriological culture and to external laboratories for
Mycoplasma spp. PCR.
The prospective observational study was approved by the Ethics
Committee of the Centre for Clinical Veterinary Medicine of Ludwig
Maximilian University (LMU) of Munich (No. 139-20-07-2018). 2.4 | 12-point clinical score

On both examination days, a total clinical score (0-12) was determined


2.1 | Inclusion criteria for each cat, using the previously published 12-point clinical score19
(Table S1). This score included information from the standardized
Client-owned cats presented for diagnostic evaluation at the LMU owner questionnaire and the findings of the clinical examination at
Clinic for Small Animal Medicine between May 2018 and July 2021, the corresponding examination time point.
19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
GAREIS ET AL. 2445

2.5 | 10-point radiographic score glucocorticoids. One cat was treated systemically with cyclosporine
(Sporimune, 5 mg/kg q24h PO) in direct combination with inhaled glu-
Thoracic radiographs were obtained from each cat on both examina- cocorticoids. Three cats received inhalative glucocorticoids only (fluti-
tion days using 2 views (left lateral and ventrodorsal or dorsoventral) casone propionate, 250 μg 1 puff q12h or salmeterol and fluticasone
in the inspiratory phase of respiratory cycle, as far as possible and tol- propionate 25 μg/125 μg, 1 puff, q12h). A bronchodilator (terbutaline,
erated by the cat. Because radiographic examinations were performed 0.05-0.1 mg/kg q8h PO) was administered in 10/24 cats initially.
exclusively on unsedated cats, optimal positioning of the patients The duration of the initial treatment was based on the clinical
could not always be achieved. A standard setting for thoracic radio- response and the duration of time it took for the cat to become accus-
graphs of kilovoltage peak (KVp) 65 and milliamperage (mA) 160 was tomed to inhalation treatment. During the study period, inhalation
used for all images. All radiographs were taken using a Fujifilm FDR treatment was started in all 24 cats. Inhalation was carried out using a
Smart X x-ray unit (FUJIFILM Europe GmbH, Ratingen, Germany), and spacing chamber and an oronasal mask (Aerokat, Trudell Medical
stored and visualized using specialized software (VetPACS-Viewer International). The aerosols used were fluticasone propionate 125 μg
7.1., Softneta UAB, Kaunas, Lithuania). All radiographs were random- 1 puff q12h in 1/24 cats, fluticasone propionate 250 μg 1 puff q12h
ized and reviewed at a later time point in Digital Imaging and Commu- in 21/24 cats, budesonide 200 μg 1 puff q12h in 1/24 cats, and sal-
nications in Medicine (DICOM) format using a DICOM viewer meterol and fluticasone propionate 25 μg/125 μg 1 puff q12h in 1/24
(RadiAnt DICOM Viewer v2021.1, Medixant, Poznan, Poland) by the cats. The dosage of the respective inhalant drug was maintained
same board-certified radiologist (SH), who was blinded to patient sig- throughout the entire study period. At the same time, PO bronchodi-
nalment, clinical signs, examination findings, examination time point, lators were discontinued and systemic glucocorticoids were gradually
and treatment. The radiographs were evaluated using a previously tapered and discontinued, because long-term treatment with inhaled
published 10-point radiographic score20 (Table S2). Pulmonary hyper- glucocorticoids alone was the aim in all study cats, leaving only 1 cat
inflation was subjectively graded as present or absent based on flat- on additional PO glucocorticoid treatment (prednisolone, 0.2 mg/kg
tening of the diaphragm, expanded lung fields, hyperlucency of the q24-48 h PO) and 1 cat on additional PO cyclosporine (Sporimune,
lungs, increased distance from the caudal margin of the cardiac silhou- 5 mg/kg q24h PO) between days 45 and day 60.
ette to the diaphragm on the lateral projection, and excessive convex-
ity of the thoracic wall, as well as increased distance between the
cardiac silhouette and the diaphragm on the ventrodorsal or dorso- 2.7 | Follow-up examination
ventral projection.
On day 60, all cats were re-presented to obtain a 12-point clinical
score and a 10-point radiographic score on the basis of the findings
2.6 | Treatment from the owner questionnaire, clinical examination, and thoracic
radiographs under treatment.
Treatment was selected individually for each study patient according
to the severity of the disease and the compliance of the cat. To facili-
tate recovery after anesthesia, 3/24 cats received a single injection of 2.8 | Statistical analysis
dexamethasone (0.4 mg/kg IV). Therapeutic agents administered
throughout the study period are listed in Table 1. A list of all thera- The statistics software SPSS version 28.0.1.0 was used for data analy-
peutic agents for each cat is provided in Table S3. Initially, 20/24 cats sis. To test for parametric distribution, the Shapiro-Wilk test was
were treated with systemic glucocorticoids (prednisolone, applied. Data was presented as mean ± SD for normally distributed
0.5-1.6 mg/kg q24h PO) followed by, or in addition to, inhaled data or median and interquartile range (IQR) for non-normally distrib-
uted data. The Wilcoxon signed-rank test was used because data was
non-normally distributed to compare the 12-point clinical score and
TABLE 1 Therapeutic agents administered over the study period. the 10-point radiographic score at both time points. Effect size of the
Wilcoxon signed-rank test as rank biserial (rrb) with 95% confidence
Number
Therapeutic agents of cats interval (Cl95%) was calculated between days 0 and 60. Effect size was
considered tiny (rrb < .05), very low (rrb = .05-.10), low (rrb = .10-.20),
Initially prednisolone, followed by fluticasone propionate 11/24
medium (rrb = .20-.30), large (rrb = .30-.40), and very large (rrb > .40).
Initially prednisolone + terbutaline, followed 8/24
by fluticasone propionate Comparison of the changes between the 2 examination time points of

Initially prednisolone, followed by budesonide 1/24 the radiographic score of the 3 inflammation subtypes was assessed
by Kruskal-Wallis test because data was non-normally distributed.
Cyclosporine + fluticasone propionate 1/24
Subsequently, P-values were corrected using the Bonferroni method
Initially terbutaline, followed by fluticasone propionate 1/24
for multiple comparisons.
Terbutaline + salmeterol and fluticasone propionate 1/24
Correlations were analyzed using Kendall rank correlation coeffi-
Fluticasone propionate only 1/24
cient r. Correlations were considered very weak (r = .00-.19), weak
19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
2446 GAREIS ET AL.

(r = .20-.39), moderately strong (r = .40-.59), strong (r = .60-.79) and 3.2 | Bronchoalveolar lavage fluid
very strong (r = .80-1.0). In addition, the coefficient of determination
r2 considered very weak (r2 = .00-.20), weak (r2 = .20-.40), moderate The median total cell count in the BALF of all the cats was 2705 cells/μL
(r2 = .40-.60), strong (r2 = .60-.80), and very strong (r2 > .80). (IQR, 1213-3275 cells/μL). The median cytological cell differentia-
For all tests, the significance level was set at P < .05. tion of the BALF was 46% eosinophils (IQR, 20%-58%), 13% neutro-
phils (IQR, 7%-43%), 33% macrophages (IQR, 17%-60%), and 0%
lymphocytes (IQR, 0%-0%). Based on previously published
3 | RESULTS classification,21 6 cats were diagnosed with eosinophilic inflamma-
tion, 2 cats with neutrophilic inflammation, and 16 cats with mixed
3.1 | Study sample inflammation.

Forty-five cats were considered suitable candidates for the study


(Figure 1). Because of ≥1 of the following, 21 cats were not included 3.3 | 12-point clinical score
in the study: upper respiratory tract disease (n = 4), positive Myco-
plasma spp. PCR (n = 8) or positive bacteriological culture (n = 4) of The cats were part of a larger study and results of the 12-point clinical
the BALF, normal BALF cytology (n = 2), missed follow-up appoint- score in a larger number of cats have been published previously.17 A
ment (n = 5), and lack of radiographs on day 60 (n = 1). comparison of the 12-point clinical score on days 0 and 60 showed
The study sample consisted of 24 cats with a mean age of 4 significant improvement in the total clinical score (5.5 [IQR, 4.4-7] vs
± 3 years (range, 1-13 years) and a mean body weight of 4.8 ± 1.4 kg 1.5 [IQR, 0-2.6]; rrb = 1.0; Cl95% [1.0, 1.0]; P < .001), coughing fre-
(range, 2.8-8.3 kg) on initial presentation. There were 14 females quency (4 [IQR, 1.4-5] vs 0.5 [IQR, 0-2]; rrb = .97; Cl95% [.92, .99];
(13 spayed, 1 intact) and 10 males (8 neutered, 2 intact). Breeds P < .001), frequency of respiratory distress (1 [IQR, 0-2] vs 0 [IQR,
included European Shorthair (n = 8), Abyssinian (n = 2), Ragdoll 0-0]; rrb = 1.0; Cl95% [1.0, 1.0]; P = .002), auscultation findings
(n = 2), Siamese (n = 1), British Shorthair (n = 1), Bengal (n = 1), Sibe- (1 [IQR, 0.9-1] vs 0 [IQR, 0-1]; rrb = .81; Cl95% [.55, .93]; P = .003),
rian Forest (n = 1), Turkish Van (n = 1), Maine Coon (n = 1), and and general condition and appetite (0 [IQR, 0-1] vs 0 [IQR, 0-0];
mixed-breed cats (n = 6). rrb = 1.0; Cl95% [1.0, 1.0]; P = .02).

Upper respiratory tract disease


(n = 4)

Other disease than or addional Posive


disease to FLAD Mycoplasma-species PCR in BALF
(n = 13) (n = 8)

Physiological BALF Posive bacterial culture in BALF


(n = 2) (n = 4)
Cats excluded
(n = 21)
Failure to appear on day 60
(n = 5)

Cats eligible for inclusion in Missing radiographs


the study (n = 1)
(n = 45)
Eosinophilic inflammaon
(n = 6)

Cats included Neutrophilic inflammaon


(n = 24) (n = 2)

Mixed inflammaon
(n = 16)

FIGURE 1 Flowchart for selection and grouping of study participants.


19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
GAREIS ET AL. 2447

3.4 | 10-point radiographic score examination time points showed no significant differences among the
3 subgroups (Tables S4 and S5).
All 24 cats showed a bronchial pattern on day 0, which was classified The results of the 10-point radiographic score are presented in
as mild (n = 14; 58.3%), moderate (n = 6; 25.0%) or severe (n = 4; Figure 3 and Table 2. The total radiographic score showed significant
16.7%). Of these, 19/24 (79.2%) showed a bronchointerstitial pattern, improvement when comparing the findings of day 0 and day
with the degree of the interstitial component varying between mild 60 (rrb = .75; Cl95% [.48, .89]; P = .01). With treatment, 19/24
(n = 9; 47.4%), moderate (n = 8; 42.1%), and severe (n = 2; 10.5%). (79.2%) cats continued to show a bronchial pattern on day 60, being
One cat (4.2%) had a focal alveolar infiltrate in the caudodorsal mild (n = 10; 52.6%), moderate (n = 8; 42.1%), or severe (n = 1;
region of the lung on day 0 (Figure 2). For this reason, bronchoscopy 5.3%). The severity of the bronchial pattern improved significantly
was performed in this cat during initial evaluation, and in addition to (rrb = .82; Cl95% [.60, .92]; P = .01). Of these cats, 14/19 (73.7%) con-
BALF, 2 mucosal biopsy samples were taken in the area of the bifurca- tinued to have a mixed bronchointerstitial pattern. The interstitial
tion for further investigation. Histopathological examination showed component was classified as mild (n = 7; 50.0%), moderate (n = 6;
granulocytic inflammation and no evidence of infectious agents or 42.3%), or severe (n = 1; 7.1%), showing significant improvement over
neoplasia, BALF cytology also disclosed moderate eosinophilic and the study period (rrb = .71; Cl95% [.36, .88]; P = .04).
neutrophilic inflammation. On day 60, 1 cat (4.2%) had a focal alveolar infiltrate in the ventral
On day 0, 10/24 (41.7%) cats had radiographic evidence of pul- aspect of the left caudal lung lobe that had not been present on day
monary hyperinflation. One cat (4.2%) had atelectasis of the right mid- 0. The alveolar infiltrate seen in the caudodorsal lung fields in 1 cat on
dle lung lobe and an equivocal caudodorsal pulmonary nodule. day 0 was no longer visible on follow-up radiographs (Figure 2). Seven
An investigation into whether the radiographic variables differed of the original 10 cats continued to show signs of pulmonary hyperin-
among cats with the 3 different subtypes of inflammation at both flation, whereas atelectasis was not noted in any of the radiographs.

F I G U R E 2 Lateral (A, C) and


ventrodorsal (B, D) thoracic
radiographs of a cat,
demonstrating improvement in
radiographic abnormalities. (A, B)
Radiographs at presentation (day
0) show a marked generalized
bronchial and unstructured
interstitial pattern with a focal
caudal dorsal alveolar infiltrate
(circle) and pulmonary
hyperinflation. The total
radiographic score was 8. (C, D)
On recheck radiographs (day 60),
the bronchial and unstructured
interstitial pattern are decreased
in severity and is now considered
moderate. The focal alveolar
pattern is no longer visible.
Pulmonary hyperinflation persists.
The total radiographic score was
5. During the radiographic
examination, the cat was
unsedated, which did not always
allow for optimal positioning.
19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
2448 GAREIS ET AL.

F I G U R E 3 Radiographic
10-point score. The line inside
the boxes demonstrates the
median total radiographic score
of all the cats included, while the
upper and lower boxes show the
IQR. The upper and lower
whiskers represent the minimum
and maximum values. The dots
show outliers. Large black
asterisks show statistical
significance: ***P-value <.001;
**P-value <.01; *P-value <.05.

T A B L E 2 Median with IQR of the radiographic 10-point score at BALF showed a weak correlation with the detection of pulmonary
both examination time points. hyperinflation on radiography (r = .36; r2 = .13; P = .04).
Radiographic 10-point score Day 0 Day 60 P value
Total radiographic score 3 (2-4) 2 (1-3.3) .01
Bronchial pattern 1 (1-2) 1 (1-2) .01
3.6 | Correlation of clinical and radiographic
Interstitial pattern 1 (1-2) 1 (0-2) .04
variables
Alveolar infiltration 0 (0–0) 0 (0-0) 1.0
Correlations of the changes in clinical and radiographic variables
Pulmonary hyperinflation 0 (0–1) 0 (0-1) .18
between the 2 examination time points are presented in Table 5. No
Lobar atelectasis 0 (0–0) 0 (0–0) .32
significant correlation was found between changes in the 12-point
Note: Bold values indicate P-value <.05. clinical score and the 10-point radiographic score.

Atelectasis seen in 1 cat on day 0 had resolved on follow-up radio-


graphs. A pulmonary nodule suspected in the same cat was no longer 4 | DI SCU SSION
visible.
No significant difference was found in the extent of improvement The purpose of our study was to evaluate whether radiographic vari-
of the radiographic variables over the study period among the 3 sub- ables in cats with naturally-occurring FLAD improve with individual
groups of inflammation (Table S6). treatment and correlate with clinical signs. The data provides evidence
of significant improvement in radiographic abnormalities with anti-
inflammatory treatment. However, no clinically relevant correlation
3.5 | Correlation between BALF cytology and with clinical improvement could be shown.
clinical and radiographic variables on day 0 Before treatment on day 0, all cats had abnormalities on
radiographic examination in addition to clinical signs. All cats had
Correlations between BALF findings and clinical and radiographic vari- bronchial or bronchointerstitial lung patterns on radiographic exami-
ables on day 0 are shown in Tables 3 and 4. A moderate correlation of nation on day 0, matching results of previous studies.9,10,22,23 Accord-
the percentage of neutrophilic granulocytes in the BALF with total ingly, in the published literature, 9% to 94% of cats with FLAD
clinical score (r = .45; r2 = .20; P = .004) and abnormal auscultation showed radiographic changes.9,22 In contrast, other authors have
findings (r = .47; r = .22; P = .004) was detected. No significant rela-
2
reported 17% to 23% of cats with FLAD as having unremarkable
tionship could be found between neutrophilic granulocytes and total thoracic radiographs.10,24
radiographic score (r = .25; r = .06; P = .12). A weak correlation was
2
Alveolar infiltrates were only documented in 1 cat at each exami-
detected between the percentage of neutrophils and the severity of nation time point, which corresponds to a previous study in which
the bronchial score (r = .37; r2 = .14; P = .03). The number of eosino- alveolar infiltration was reported rarely.10 In contrast, another investi-
philic granulocytes in BALF neither correlated with the total clinical gation showed alveolar patterns in 44% of cats with lower airway dis-
score (r = .21; r2 = .04; P = .17) nor with the total radiographic ease.25 Cats responding to antibiotics were included in that study, and
score (r = .04; r2 = .00; P = .8). concurrent bacterial respiratory tract disease resulting in alveolar pat-
The number of macrophages in BALF showed a weak negative terns could not be excluded.
correlation with coughing frequency (r = .38; r2 = .14; P = .02) and On day 0, lung hyperinflation was detected in 41.7% cats, with a
the bronchial score (r = .38; r2 = .14; P = .02). Total cell count in more frequent occurrence compared with previous reports.10,24,25
19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
GAREIS ET AL. 2449

TABLE 3 Correlation between the BALF cytology findings and the clinical 12-point score on day 0.

Clinical 12-point score


Total clinical Coughing Respiratory Auscultation General condition/
BALF cytology score frequency distress score appetite
Total cell count (cells/μL) r = .02 r = .012 r = .02 r = .11 r = .21
r2 = .00 r2 = .00 r2 = .00 r2 = .01 r2 = .04
Eosinophils (%) r = .21 r = .08 r = .21 r = .32 r = .28
r2 = .04 r2 = .01 r2 = .04 r2 = .10 r2 = .08
Neutrophils (%) r = .45 r = .22 r = .09 r = .47 r = .17
r2 = .20 r2 = .05 r2 = .01 r2 = .22 r2 = .03
Macrophages (%) r = .17 r = .38 r = .18 r = .11 r = .19
r2 = .03 r2 = .14 r2 = .03 r2 = .01 r2 = .04
Lymphocytes (%) r = .09 r = .09 r = .03 r = .09 r = .32
r2 = .01 r2 = .01 r2 = .00 r2 = .01 r2 = .10

Note: Bold values indicate P-value <.05.

TABLE 4 Correlation between the BALF cytology findings and the radiographic 10-point score on day 0.

Radiographic 10-point score


Total radiographic Bronchial Interstitial Alveolar Pulmonary Lobar
BALF cytology score pattern pattern infiltration hyperinflation atelectasis
Total cell count (cells/μL) r = .10 r = .38 r = .05 r = .26 r = .36 r = .01
r2 = .01 r2 = .14 r2 = .00 r2 = .07 r2 = .13 r2 = .00
Eosinophils (%) r = .04 r = .05 r = .13 r = .04 r = .12 r = .04
r2 = .00 r2 = .00 r2 = .02 r2 = .00 r2 = .01 r2 = .00
Neutrophils (%) r = .25 r = .37 r = .20 r = .17 r = .06 r = .14
r2 = .06 r2 = .14 r2 = .04 r2 = .03 r2 = .00 r2 = .02
Macrophages (%) r = .29 r = .38 r = .18 r = .24 r = .27 r = .14
r2 = .08 r2 = .14 r2 = .03 r2 = .06 r2 = .07 r2 = .02
Lymphocytes (%) r = .09 r = .01 r = .15 r = .08 r = .07 r = .08
r2 = .01 r2 = .01 r2 = .02 r2 = .01 r2 = .01 r2 = .01

Note: Bold values indicate P-value <.05.

T A B L E 5 Correlation between the changes in the clinical 12-point score and the radiographic 10-point score between the two examination
time points.

Changes in radiographic 10-point score


Total radiographic Bronchial Interstitial Alveolar Pulmonary Lobar
Changes in clinical 12-point score score pattern pattern infiltration hyperinflation atelectasis
Total clinical score r = .24 r = .12 r = .16 r = .29 r = .10 r = .28
r2 = .06 r2 = .04 r2 = .03 r2 = .09 r2 = .11 r2 = .08
Coughing frequency r = .35 r = .03 r = .02 r = .26 r = .24 r = .15
r2 = .12 r2 = .00 r2 = .00 r2 = .07 r2 = .06 r2 = .02
Respiratory distress r = .10 r = .05 r = .07 r = .12 r = .06 r = .08
r2 = .01 r2 = .00 r2 = .01 r2 = .01 r2 = .00 r2 = .01
Auscultation score r = .21 r = .02 r = .15 r = .00 r = .17 r = .32
r2 = .04 r2 = .00 r2 = .02 r2 = .00 r2 = .03 r2 = .10
General condition/appetite r = .27 r = .30 r = .25 r = .00 r = .04 r = .12
r2 = .07 r2 = .09 r2 = .06 r2 = .00 r2 = .00 r2 = .01

Note: All correlations were not statistically significant.


19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
2450 GAREIS ET AL.

The reason for more frequent hyperinflation, defined as an abnormal borders of the bronchial walls into the pulmonary interstitium,28 and
increase in lung volume at the end of tidal expiration,26 in our study is therefore require more time to recover. For this hypothesis to be sup-
unclear. Lower airway obstruction can lead to hyperinflation of the ported, it would be necessary to examine follow-up radiographs after
lungs, because the affected cats are unable to fully exhale because of a longer period of treatment.
narrowed airways, resulting in air trapping and causing expiratory Although not significant, the number of patients with hyperinfla-
respiratory distress.6,10 Thus, during episodes of respiratory distress, tion and atelectasis on radiographic examination decreased over the
lung hyperinflation may be present, but between these episodes it study period. Because hyperinflation was still radiographically visible
may remain undetected radiographically.27 Discrepancies among dif- in 7/10 originally affected cats on day 60 despite treatment, in some
ferent study results could be explained by differences in clinical stabil- cases treatment was modified on day 60 by adding a bronchodilator.
ity when the radiographs were taken. Hyperinflation on radiographic A possible explanation for the fact that some cats continued to show
imaging may have been more frequently detected, because only cats radiographic hyperinflation even with treatment could be discontinua-
with obvious current clinical signs (including episodes of respiratory tion of the bronchodilator after several weeks, because bronchodila-
distress) were included in our study, and 70% of cats with radio- tors were administered only initially in most cases. However, because
graphic findings of hyperinflation on day 0 showed obvious signs of these cats showed further clinical improvement on day 60, with com-
respiratory distress before enrollment. Another study observed lung plete absence of respiratory distress in 6/7 cats and existing but
hyperinflation in cats with FLAD as the third most common radio- marked improvement in respiratory distress episodes in 1/7 cats, it is
graphic abnormality,7 which is more consistent with our present data. also possible that radiographic findings lag behind clinical status, and
This finding is somewhat subjective, and may be variably identified by may further improve with prolonged consistent treatment. In addition,
different radiologists. ongoing subclinical inflammation could not be ruled out in our study,
Some authors have reported that approximately 10% of cats with because a second BALF was not obtained on day 60 because of the
FLAD have atelectasis of the middle right lung lobe on radiographs, risk involved in repeating the procedure under anesthesia in client-
because of its dorsoventral orientation within the bronchial tree, owned cats.
3
which allows mucus to accumulate easily. Our study identified this Cats with positive Mycoplasma spp. PCR on BALF examination
radiographic abnormality in only 1 cat on day 0. However, it was no were excluded from the study, because the pathogenicity and clinical
longer visible during treatment, consistent with results reported in relevance of these microorganisms in the context of FLAD are not yet
other studies.10,25 clearly understood, and our aim was to investigate a population that
Comparing the prevalence of hyperinflation and atelectasis on was as homogeneous as possible. Whether the absence of Myco-
radiographs among studies is challenging, because these pathological plasma ssp. contributed to greater improvement in radiographic find-
changes often were not reported in prior investigations. Furthermore, ings in our study and whether Mycoplasma spp. in the lower airways
a standardized radiographic score would be necessary for direct leads to more severe abnormalities on radiographs cannot be
comparison. answered within the context of this study and should be further
In addition to improvement in clinical variables, the total radio- investigated in the future.
graphic score improved significantly during treatment. This finding A correlation was found between the percentage of neutrophilic
matches results of a previous investigation of research cats suffering granulocytes in BALF and total clinical score, auscultation abnormalities
from mild CB, treated with inhaled fluticasone (250 μg; q24h), after and severity of bronchial lung pattern on day 0. This finding contradicts
2 weeks of treatment.16 Besides the total score, our current results a previous study that did not show a correlation between clinical or
show clinically relevant improvement in both bronchial and interstitial radiological findings and BALF variables.20 In addition, we were able to
lung patterns. In comparison, a previous study15 did not report any show a negative correlation between percentage of macrophages in the
improvement in radiographic variables in 9 cats with FLAD after PO BALF and coughing frequency and severity of bronchial pattern on radi-
(prednisolone, 5 mg q12h; and decrease after 14 days to predniso- ography, which suggests that a higher coughing frequency and more
lone, 5 mg q24h in 4/9 cats) or combined PO and inhaled (predniso- severe bronchial pattern are associated with lower numbers of macro-
lone, 5 mg q24h PO for 7 days, followed by fluticasone 110 μg q12h phages in the BALF. Because macrophages are the predominant cell
in 5/9 cats) glucocorticoid treatment in a preliminary study. Because type in the BALF in healthy cats,5 this result is not surprising. Thus, in
the follow-up examination during treatment also took place after cats suffering from FLAD with evidence of coughing and bronchial lung
8 weeks, it is unclear why the results differed from those of our study. pattern on radiographs, lower numbers of macrophages and higher num-
The small study sample and potential differences in disease severity bers of neutrophils or eosinophils are to be expected in BALF cytology.
15
could account for the discrepancy. The total cell count in the BALF correlated only with the prevalence of
Our study showed more improvement in the bronchial lung pat- lung hyperinflation. This observation contradicts the results of a previ-
tern as compared to the interstitial lung pattern. This result may indi- ous study in which total cell count showed a significant correlation with
cate that bronchial changes improve more rapidly with adequate almost all radiographic scores in experimentally-induced bronchial
treatment than do interstitial changes. A possible explanation might inflammation in cats.29 However, this study included both Ascaris suum-
be that cats with advanced FLAD are more likely to show interstitial sensitized cats, as well as a healthy control group, which limits compari-
lung patterns as a result of extension of the inflammation over the son with the findings of our study.
19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
GAREIS ET AL. 2451

To investigate the relationship between clinical signs and radio- significantly. However, we failed to show a correlation between the
logical findings in cats with FLAD, the changes in the 12-point clinical improvement of clinical and radiographic findings. The results indicate
score and the 10-point radiographic score over the study period were that, in addition to clinical signs, repeated radiographic examination
analyzed for correlation. No clinically relevant correlation was found can be used to assess treatment response in cats with FLAD. How-
between the clinical and radiographic variables, in accordance with ever, differences exist in how clinical and radiographic variables
results of previous studies.24,25 In humans with asthma, a correlation improve in cats with FLAD undergoing treatment.
between radiographic abnormalities and clinical signs also could not
be proven.30 This result stresses the importance of reconciling radio- ACKNOWLEDG MENT
graphic abnormalities with medical history, physical examination and No funding was received for this study. Part of the study was pre-
laboratory data at all times. Why the changes in clinical and radio- sented orally at the European College of Veterinary Internal
graphic variables failed to show a relevant correlation despite Medicine – Companion Animals (ECVIM-CA) 32rd Annual Congress,
improvement in both scores over the study period remains unknown. September 01-03, 2022, Gothenburg, Sweden. Open Access funding
A possible explanation could be that clinical signs likely respond faster enabled and organized by Projekt DEAL.
to adequate treatment compared to radiological findings. Seven cats
continued to show pulmonary hyperinflation radiographically at the CONFLICT OF INTEREST DECLARATION
follow-up examination despite substantial clinical improvement, which Authors declare no conflict of interest.
supports this assumption. Further evaluation of this finding would
require more frequent follow-up examinations at shorter time inter- OF F-LABEL ANTIMI CROBIAL DECLARATION
vals after initiation of treatment, which would be challenging in client- Authors declare no off-label use of antimicrobials.
owned cats.
However, radiographic findings did improve as clinical signs INSTITU TIONAL ANIMAL C AR E AND USE COMMITTEE
improved, suggesting that radiographic examination is a sensitive tool (IACUC) OR OTHER APPROVAL DECLARATION
for monitoring treatment response in cats with FLAD. Assessing ther- Approved by the Ethics Committee of the Centre for Clinical Veteri-
apeutic response by radiographic examination makes sense especially nary Medicine of Ludwig Maximilian University, Munich (No. 139-
for cats where clinical evaluation may be limited (eg, in cats that spend 20-07-2018) and informed owner consent was obtained for all cats
most of the day unattended or outdoors). In addition, it is known that before enrolment.
clinical signs can vary in cats with FLAD. Radiographic examination
therefore may help assess treatment response and optimization in HUMAN E THICS APPROVAL DECLARATION
clinically healthy cats. Authors declare human ethics approval was not needed for this study.
The lack of a standardized treatment protocol is a limitation of
our study. We deliberately decided against a standardized approach OR CID
to treatment, because individualized treatment is more responsive to Hannah Gareis https://orcid.org/0000-0002-5740-6023
the individual needs of the cats, as well as the owners. This approach
mimics the situation in clinical practice, in which an individual RE FE RE NCE S
approach to each patient is essential. In addition, all radiographs were 1. Reinero CR. Feline asthma. In: Noli C, Foster A, Rosenkrantz W, eds.
interpreted by the same radiologist, which may involve a certain Veterinary Allergy. 1st ed. West Sussex: John Wiley & Sohn; 2014:
degree of subjectivity, and it was not possible to investigate interob- 239-245.
2. Byers CG, Dhupa N. Feline bronchial asthma: pathophysiology and
server variability. Furthermore, radiographic imaging during the inspi-
diagnosis. Compend Contin Educ Pract Vet. 2005;27:418-425.
ratory phase of the respiratory cycle is not always possible in cats that 3. Padrid P. Chronic bronchitis and asthma in cats. In: Bonagura JD,
are awake, which may have influenced interpretation of the radio- ed. Current Veterinary Therapy XIV. Missouri: Saunders Elvisier; 2009:
graphs. Because radiographic examinations were performed exclu- 650-658.
4. Dye JA, McKiernan BC, Rozanski EA, et al. Bronchopulmonary disease
sively on unsedated awake cats, optimal positioning could not always
in the cat: historical, physical, radiographic, clinicopathologic, and pul-
be guaranteed, which also may have had an impact on the quality of monary functional evaluation of 24 affected and 15 healthy cats.
the radiographs. However, this situation reflects the reality in J Vet Intern Med. 1996;10:385-400.
veterinary practice in many countries, in which cats are usually radio- 5. Reinero CR, DeClue AE. Feline tracheobronchial disease. In:
Fuentes VL, Johnson LR, Dennis S, eds. BSAVA Manual of Canine and
graphed unsedated.
Feline Cardiorespiratory Medicine. 2nd ed. Gloucester: British Small
Animal Veterinary Association; 2010:280-284.
6. Bay JD, Johnson LR. Feline bronchial disease/asthma. In: King LG,
5 | C O N CL U S I O N ed. Textbook of Respiratory Disease in Dogs and Cats. St Louis: Saun-
ders; 2004:388-396.
7. Gadbois J, d'Anjou MA, Dunn M, et al. Radiographic abnormalities in
In addition to clinical signs, radiographic abnormalities could be
cats with feline bronchial disease and intra- and interobserver vari-
detected in all cats with FLAD at initial presentation. With individual- ability in radiographic interpretation: 40 cases (1999-2006). J Am Vet
ized treatment, both clinical and radiographic variables improved Med Assoc. 2009;234:367-375.
19391676, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jvim.16874 by Cochrane Mexico, Wiley Online Library on [02/03/2024]. 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
2452 GAREIS ET AL.

8. Padrid P. Feline asthma: diagnosis and treatment. Vet Clin North Am 22. Grotheer M, Hirschberger J, Hartmann K, Castelletti N, Schulz B.
Small Anim Pract. 2000;30:1279-1293. Comparison of signalment, clinical, laboratory and radiographic
9. Lee EA, Johnson LR, Johnson EG, Vernau W. Clinical features and radio- parameters in cats with feline asthma and chronic bronchitis. J Feline
graphic findings in cats with eosinophilic, neutrophilic, and mixed airway Med Surg. 2020;22:649-655.
inflammation (2011-2018). J Vet Intern Med. 2020;34:1291-1299. 23. Lin CH, Wu HD, Lee JJ, Liu CH. Functional phenotype and its correla-
10. Corcoran BM, Foster DJ, Fuentes VL. Feline asthma syndrome: a ret- tion with therapeutic response and inflammatory type of bronchoal-
rospective study of the clinical presentation in 29 cats. J Small Anim veolar lavage fluid in feline lower airway disease. J Vet Intern Med.
Pract. 1995;36:481-488. 2015;29:88-96.
11. Moise NS, Wiedenkeller D, Yeager AE, Blue JT, Scarlett J. Clinical, radio- 24. Adamama-Moraitou KK, Patsikas MN, Koutinas AF. Feline lower air-
graphic, and bronchial cytologic features of cats with bronchial disease: way disease: a retrospective study of 22 naturally occurring cases
65 cases (1980-1986). J Am Vet Med Assoc. 1989;194:1467-1473. from Greece. J Feline Med Surg. 2004;6:227-233.
12. Moses BL, Spaulding GL. Chronic bronchial disease of the cat. Vet Clin 25. Foster SF, Allan GS, Martin P, Robertson ID, Malik R. Twenty-five
North Am Small Anim Pract. 1985;15:929-948. cases of feline bronchial disease (1995–2000). J Feline Med Surg.
13. Cocayne CG, Reinero CR, DeClue AE. Subclinical airway inflammation 2004;6:181-188.
despite high-dose oral corticosteroid therapy in cats with lower air- 26. Gibson GJ. Pulmonary hyperinflation a clinical overview. Eur Respir J.
way disease. J Feline Med Surg. 2011;13:558-563. 1996;9:2640-2649.
14. Trzil JE. Feline asthma: diagnostic and treatment update. Vet Clin 27. Dye JA. Feline bronchopulmonary disease. Vet Clin North Am Small
North Am Small Anim Pract. 2020;50:375-391. Anim Pract. 1992;22:1187-1201.
15. Verschoor-Kirss M, Rozanski EA, Sharp CR, et al. Treatment of natu- 28. Suter PL, Lord PF. Methods in radiographic diagnosis. In: Suter P,
rally occurring asthma with inhaled fluticasone or oral prednisolone: a ed. Thoracic Radiography: a Text Atlas of Thoracic Diseases of the Dog
randomized pilot trial. Can J Vet Res. 2021;85:61-67. and Cat. Switzerland: Wettswill; 1984:77-126.
16. Kirschvink N, Leemans J, Delvaux F, et al. Inhaled fluticasone reduces 29. Kirschvink N, Kersnak E, Leemans J, et al. Effects of age and allergen-
bronchial responsiveness and airway inflammation in cats with mild induced airway inflammation in cats: radiographic and cytologic cor-
chronic bronchitis. J Feline Med Surg. 2006;8:45-54. relation. Vet J. 2007;174:644-651.
17. Gareis H, Hörner-Schmid L, Zablotski Y, Palic J, Schulz B. Evaluation 30. Blair DN, Coppage L, Shaw C. Medical imaging in asthma. J Thorac
of barometric whole-body plethysmography for therapy monitoring Imaging. 1986;1:23-35.
in cats with feline lower airway disease. PloS One. 2022;17:
e0276927.
18. Stursberg U. Felines Asthma und chronische Bronchitis: Untersuchungen SUPPORTING INF ORMATION
zu Anamnese, Allergiediagnostik und Therapie mit Propentofyllin. Tierärz-
Additional supporting information can be found online in the Support-
tliche Fakulätet. München: Ludwig-Maximilians-Universität; 2010.
19. Lin CH, Lee JJ, Liu CH. Functional assessment of expiratory flow pat- ing Information section at the end of this article.
tern in feline lower airway disease. J Feline Med Surg. 2014;16:
616-622.
20. Allerton FJ, Leemans J, Tual C, et al. Correlation of bronchoalveolar How to cite this article: Gareis H, Hörner-Schmid L,
eosinophilic percentage with airway responsiveness in cats with Zablotski Y, Palic J, Hecht S, Schulz B. Correlation of clinical and
chronic bronchial disease. J Small Anim Pract. 2013;54:258-264.
radiographic variables in cats with lower airway disease. J Vet
21. Nafe LA, DeClue AE, Reinero CR. Storage alters feline bronchoalveo-
lar lavage fluid cytological analysis. J Feline Med Surg. 2011;13:
Intern Med. 2023;37(6):2443‐2452. doi:10.1111/jvim.16874
94-100.

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