Do inhaled or oral glucocorticoids more effectively control feline asthma?

a Knowledge Summary by

Savannah Clare Williams BVMedSci (Hons) BVM BVS PGDip(VCP) MRCVS ^1*

¹University of Bristol, Langford Vets, Langford, Somerset, BS40 5DU
^*Corresponding Author (savannah_williams@hotmail.com)

Clinical scenario

You are presented with a 4 year old cat with a 5 month history of intermittent coughing alongside periods of acute wheezing and respiratory difficulty. Clinical examination of the cat is unremarkable. Investigations inclusive of bloodwork, thoracic radiography and a bronchoalveolar lavage reveal an eosinophilia, bronchial pattern, and eosinophilic infiltrate, respectively. A faecal Baermann test was negative for lungworm larvae. A diagnosis of feline asthma is made. You wish to start the cat on glucocorticoids however, you are unsure whether oral therapy or inhalant therapy is more effective at controlling clinical signs.

The evidence

Database searches identified three papers offering evidence to answer the PICO question (Verschoor-Kirss et al., 2021; Leemans et al., 2012; and Reinero et al., 2005) once duplicates had been removed. All studies were prospective in nature with two of them following a crossover design (Leemans et al., 2012; and Reinero et al., 2005). None of the studies were directly comparable due to differences in study population type and differing drug regimens, although the outcomes measured were similar.

Summary of the evidence

Appraisal, application and reflection

All three studies used a reduction in airway resistance and reduction in airway eosinophilia as measures of treatment success (Verschoor-Kirss et al. 2021; Leemans et al. 2012; and Reinero et al. 2005).

Pulmonary function testing of asthmatic cats offers a non-invasive means of assessing response to therapy, and in the study by (Leemans et al. 2012) barometric whole-body plethysmography was used in unrestrained conscious cats to assess changes in airway resistance. In contrast, Reinero et al. (2005) and Verschoor-Kirss (2021), anaesthetised cats before airway challenge commenced and the airway’s response was assessed. Leemans et al. (2012) and Reinero et al. (2005) did not find a significant difference in the reduction of airway resistance among treatment groups. Meanwhile Verschoor-Kirss (2021) found that there was a greater reduction in airway resistance with oral glucocorticoid treatment compared to baseline than with inhaled therapy. Although this study does highlight that cats in the inhaled treatment group started with higher baseline resistance than those in the oral group.

Regardless of the study design all studies found that when an oral or inhaled therapy was used, treatment resulted in a reduction in airway eosinophilia. However, only Leemans et al. (2012) found the decrease in BAL fluid eosinophil percentage to be more significant with oral therapy compared to inhaled therapy alone. Interestingly, when salbutamol was used concurrently with the inhaled therapy in this study, they found a significant decrease in BAL fluid eosinophil percentage also (Leemans et al. 2012).

An additional method that was used to evaluate treatment response in the asthmatic cat cohorts, was the change in radiographic appearance of the lungs (determined by a clinical score). Verschoor-Kirss (2021) and Leemans et al. (2012) used changes in the radiographic appearance of the lung as a study outcome. Thoracic radiographs were assessed before and after treatment administration and assigned a score. However, no significant difference was detected between scores before or after oral or inhaled treatment in either study.

Two of the three papers chose to assess fluticasone propionate as the inhaled glucocorticoid and prednisolone as the oral glucocorticoid (Verschoor-Kirss et al. 2021; and Leemans et al. 2012) whilst Reinero et al. (2005) assessed flunisolide and prednisone. Despite two of the studies using the same medications, they were not cross comparable as the doses of the drugs, and length of time for which cats received the oral and / or inhaled glucocorticoid treatment varied greatly. Treatment duration varied from 4 days (Leemans et al. 2012) to 8 weeks (Verschoor-Kirss et al. 2021). Future studies could consider using varying concentrations of each treatment on the same study population to determine the minimum effective dose to control clinical signs associated with asthma.

Verschoor-Kirss et al. (2021) was the only study that assessed a population of naturally asthmatic cats. Clinically their response to treatment is more likely to reflect that of owned asthmatic cats. The treatment protocol in this study differed from the other studies; oral glucocorticoid treatment was given concurrently with the inhalant therapy for 1 week before inhalant therapy was continued exclusively. Whilst this makes it more difficult to determine the efficacy of fluticasone as a sole therapy, this treatment protocol is more likely to be reflective of a feline asthma treatment protocol prescribed in general practice.

All the clinical studies had low numbers of feline participants and study duration was short. The small cohort numbers reduce the statistical power of each paper’s results and consequently make it difficult to draw confident conclusions. Power analysis would be beneficial before performing further prospective, randomised, blinded studies.

Overall, there is a weak pool of evidence available to determine if oral or inhaled glucocorticoid treatment is more effective at managing the airway inflammation associated with feline asthma.

Methodology Section

Search Strategy
Databases searched and dates covered:	CAB Abstracts 1973 to 2021 Week 46 (via the OVID platform) Ovid MEDLINE® 1946 to present (via the OVID platform)
Search strategy:	The same search was used for both databases: (cat or cats or feline*).mp. or exp cats/   (asthma* or wheez* or respiratory hypersensitiv* or airway hyper responsiveness or airway hyper-responsiveness or bronchospasm* or bronchial spasm*).mp. or exp asthma/ (glucocorticoid* or glucocorticosteroid*).mp. or exp glucocorticoids/ 1 and 2 and 3
Dates searches performed:	10 Apr 2022

Exclusion / Inclusion Criteria
Exclusion:	Articles where the full text was not available in English; articles not relevant to the PICO question; articles listed as: a single case report, conference proceedings, book chapter, or review article.
Inclusion:	Articles written in English; relevant to PICO question; more than one animal; studies that used an inhaled and oral glucocorticoid as the only treatment.

Search Outcome
Database	Number of results	Excluded – Not relevant to the PICO question	Excluded – Not available in English	Excluded – Book chapter / conference proceeding / single case report / review article	Total relevant papers
CAB Abstracts	33	17	5	10	1
OVID Medline®	55	50	1	1	3
Total relevant papers when duplicates removed					3

Savannah Clare Williams: https://orcid.org/0000-0001-8341-9074

The author declares no conflicts of interest.

1. Leemans, J., Kirschvink, N., Clercx, C., Snaps, F. & Gustin, P. (2012). Effect of short-term oral and inhaled corticosteroids on airway inflammation and responsiveness in a feline acute asthma model. The Veterinary Journal. 192(1), 41–48. DOI: https://doi.org/10.1016/j.tvjl.2011.01.020
2. Reinero, C. R., Decile, K. C., Byerly, J. R., Berghaus, R. D., Walby, W. F., Berghaus, L. J., Hyde, D. M., Schelegle, E. S. & Gershwin, L. J. (2005). Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma. American Journal of Veterinary Research. 66(7), 1121–1127. DOI: https://doi.org/10.2460/ajvr.2005.66.1121
3. Verschoor-Kirss, M., Rozanski, E. A., Sharp, C. R., Oura, T. J., Egan, A., Bain, P. & Knoll, J. (2021). Treatment of naturally occurring asthma with inhaled fluticasone or oral prednisolone: a randomized pilot trial. The Canadian Journal of Veterinary Research. 85(1), 61–67.