Page 333 - Clinical Small Animal Internal Medicine

30 Feline Bronchial Asthma 301

inhibitor to reduce airway remodeling; and prevent the Methylxanthine bronchodilators can be used in
VetBooks.ir downregulation of beta‐adrenergic receptors. conjunction with antiinflammatory therapy for chronic
management of refractory disease. Theophylline is the
Orally administered glucocorticoids are used in the
initial management of stable asthmatics. Prednisolone is
preferred over prednisone in cats because of impaired methylxanthine derivative that has been studied most
extensively in cats. The mechanism by which methylx-
hepatic bioconversion of prednisone. No standardized anthines induce bronchodilation is postulated to be
dosing regimen and tapering schedule exists for the use related to inhibition of phosphodiesterase, which leads
of glucocorticoids in the management of feline bron- to increased intracellular cAMP and, subsequently,
chial asthma. Patients are typically started on therapy at smooth muscle relaxation. However, theophylline does
doses near or at the immunosuppressive range (1–2 mg/ not inhibit phosphodiesterase at therapeutic concentra-
kg PO q12h). Long‐term therapy with systemic gluco- tions. Inhibition of adenosine or interference with
corticoids can be associated with numerous undesirable intracellular calcium levels may instead explain the
effects such as polyuria, polydipsia, polyphagia, weight bronchodilatory effects of these agents. Theophylline
gain, alopecia, thinning of the skin, increased suscepti- also prevents mast cell degranulation, reduces micro-
bility to infections, and the development of diabetes vascular leakage, and increases respiratory muscle
mellitus. Systemic steroids can also exacerbate underly- strength. When administered in the evening, sustained‐
ing cardiac disease. To minimize these complications, release theophylline achieves higher peak plasma con-
the initial prednisolone dose is tapered by 25–50% once centrations compared to morning administration. The
clinical signs have resolved and after at least seven days recommended dose of slow‐release preparations is
of therapy. 20–50 mg/kg PO q24h. Adverse effects associated with
Inhaled glucocorticoids are associated with negligible methylxanthine derivatives include central nervous
adverse effects compared to those seen with systemic system stimulation, tachyarrhythmias, increased gastric
therapy and are a very effective means of managing acid secretion, and diuresis. Because of this, methylxan-
feline asthma long term. Inhaled steroids are minimally thines should be used cautiously in patients with preex-
absorbed into the systemic circulation and undergo isting cardiac disease, seizure disorders, hyperthyroidism,
extensive first‐pass metabolism. Fluticasone propionate and gastric ulcers. Long‐acting bronchodilators such as
is the most commonly prescribed inhaled glucocorti- theophylline should be used adjunctively with steroid
coid in veterinary medicine. It has the longest receptor therapy to achieve improved control of clinical signs in
residency time and greatest lipophilicity of the inhaled patients that do not completely respond to glucocorti-
glucocorticoids as well as a high therapeutic index. coid therapy alone.
Treatment with inhaled fluticasone has been shown to Ciclosporin has been promoted for management of
reduce airway inflammation and hyperresponsiveness feline asthma that is refractory to glucocorticoid and
in cats with naturally occurring lower airways disease bronchodilator therapy. A calcineurin inhibitor, ciclo-
and in cats with experimentally induced asthma. sporin inhibits T cell activation and proliferation by inter-
Suppression of the hypothalamic‐pituitary‐adrenocorti- fering with the transcription of genes related to cytokine
cal axis has been demonstrated in healthy cats following production, particularly IL‐2. In an experimental model
treatment with inhaled glucocorticoids, but significant of feline asthma, treatment with ciclosporin prior to and
suppression of the systemic immune response was not during chronic antigen challenge decreased the amount
noted. Fluticasone doses of 44 μg, 110 μg, and 220 μg of IL‐2 secreted from peripheral blood lymphocytes,
q12h were shown to reduce airway inflammation in prevented an increase in airway hyperresponsiveness
experimental models of feline asthma with similar effi- after chronic antigen stimulation, and resulted in reduced
cacy. Fluticasone is available in a metered dose inhaler airway smooth muscle thickness and mucosal eosinophil
formulation and can be administered to cats using a infiltration histologically compared to untreated cats.
chamber and facemask as with inhaled albuterol. Following acute antigen challenge in the same model,
Systemic steroid therapy should be continued during pretreatment with ciclosporin did not prevent mast cell
the first 14 days of treatment with fluticasone to allow degranulation or an increase in lung resistance. Despite
the inhaled glucocorticoid to reach full effect. The oral this, tracheal smooth muscle harvested from these artifi-
glucocorticoid dose can then be gradually tapered and cially sensitized cats did not contract in response to anti-
eventually discontinued while inhalant therapy is con- gen exposure when incubated with ciclosporin in vitro.
tinued long term. Inhaled budesonide (400 μg q12h) has Given these differential findings, ciclosporin should be
also been evaluated in asthmatic cats and has been reserved for patients with a poor response to standard
shown to reduce airway responsiveness while causing asthma therapies. An initial dose of 10 mg/kg PO q12h is
suppression of the hypothalamic‐pituitary‐adrenal axis recommended with the goal of achieving blood trough
in a subset of treated cats. levels of 500–1000 ng/mL. Adverse effects associated