猫特应性皮炎综合征的治疗-系统性回顾（3）

王帆

Treatment of the feline atopic syndrome – a systematic review

猫特应性皮炎综合征的治疗-系统性回顾

作者：Ralf S. Mueller* , Tim Nuttall† , Christine Prost‡, Bianka Schulz* and Petra Bizikova§

翻译：王帆

Bronchodilators

支气管扩张剂

Analysis of evidence

证据分析

One study evaluated salbutamol, ipratropium bromide and the combination of those two drugs in cats sensitised to ovalbumin and to A. suum compared to control cats. In another study, the same drugs were used in a doubleblinded, placebo-controlled cross-over design in A. suumsensitised cats. In a clinical study including 19 cats with naturally occuring bronchial disease, therapy with lowdose prednisolone was supplemented with propentofylline in 10 cats.

一项研究评估了沙丁胺醇、异丙托溴铵和这两种药物联合使用对卵清蛋白和猪蛔虫敏感的猫与对照组猫的效果。在另一项研究中，同样的药物被用于对猪蛔虫敏感的猫的双盲、安慰剂对照交叉设计。在一项包括19只自然发生支气管疾病的猫的临床研究中，用小剂量泼尼松龙治疗10只猫并辅以丙戊茶碱。

Analysis of efficacy

疗效分析

In the first study, cats sensitised to ovalbumin (n=6), to A. suum (n=6) and nonsensitised control cats (n=6) were evaluated. Salbutamol (100 mcg, two puffs), ipratropium bromide (20 mcg, two puffs) or a combination of salbutamol and ipratropium bromide (120 mcg/20 mcg, two puffs) were administrated to the conscious cats by use of a pressurized metered-dose inhaler and a spacing chamber connected through an inspiratory valve to a facemask. Salbutamol/ipratropium bromide reduced BAL-induced bronchoconstriction in the cats sensitised to A. suum, and not in the cats sensitised to ovalbumin or control cats. By contrast, salbutamol or ipratropium bromide alone did not lead to any significant changes. In the cross-over study with five cats sensitised to A. suum, enhanced pause, an estimator of airflow limitation measured by BWBP, was repeatedly assessed within 120 min following the administration of each treatment protocol. Responses to inhaled medications were evaluated by calculating the area under the time–response curves (AUC) from 0 to 60 or 120 min after drug administration (AUC0–60, AUC0–120), as well as the times required for half-recovery or for returning to nearly basal conditions. There was no difference in time-related bronchodilating effects between 100 mcg salbutamol, 20 mcg ipratropium bromide, a combination of the two treatments, and the nontreated control. Cats treated with a combination of propentophylline and prednisolone significantly improved in their auscultation scores, respiratory pattern scores and radiological bronchial markings score over the observation period, and they coughed less and were more active at the end of the study compared to the cats treated with prednisolone alone.

在第一项研究中，对卵清蛋白过敏的猫(6只)，对猪蛔虫过敏(6只)和未过敏对照猫(6只)进行了评估。沙丁胺醇(100 mcg, 吸入2次)、异丙托溴铵(20 mcg, 吸入2次)或沙丁胺醇和异丙托溴铵的组合(120 mcg/20mcg, 吸入2次)通过加压计量吸入器和通过吸入阀连接到面罩的间隔室给予清醒患猫。沙丁胺醇/异丙托溴铵减少了对猪蛔虫敏感的猫的BAL诱导的支气管狭窄，而对卵清蛋白敏感的猫或对照组的猫则没有。相比之下，单独使用沙丁胺醇或异丙托溴铵并没有导致任何显著的变化。在5只猫对猪蛔虫敏感的交叉研究中，强化暂停(通过BWBP测量的气流限制估计数值)在每个治疗方案实施后的120分钟内反复评估。通过计算给药后0-60或0-120 min时间响应曲线下面积(AUC) (AUC0 60、AUC0 120)以及半恢复或恢复到基本状态所需的时间来评估吸入药物的反应。100 mcg沙丁胺醇、20 mcg异丙托溴铵、两种药物联合治疗和非治疗对照在时间相关的支气管扩张效果上没有差异。猫使用丙戊茶碱联合泼尼松龙治疗，与单独使用泼尼松龙治疗的患猫相比，在观察期间的听诊评分、呼吸模式评分和支气管标记影像评分显著改善,患猫咳嗽次数减少，研究结束时表现更活跃。

Adverse effects

副作用

No adverse reactions occurred in one study, adverse effects were not mentioned in two.

一项研究中未出现副反应，两项研究中未提及副反应。

Recommendations

建议

Although bronchodilators are frequently recommended for the treatment of feline asthma, the two evaluated studies provided no evidence supporting the use of bronchodilators in asthmatic cats (QOE2; SOR B). Moreover, both trials were with cats experimentally sensitised in the laboratory and studies evaluating bronchodilators in cats with naturally occurring asthma are lacking. Despite this, inhaled bronchodilators are recommended for management of acute asthmatic episodes and for long-term treatment of feline asthma alongside inhaled steroids (QOE3; SOR C). Clearly, further studies on the efficacy of bronchodilators are needed.

虽然经常推荐使用支气管扩张剂治疗猫哮喘，但两项评估性研究没有提供证据支持使用支气管扩张剂治疗哮喘患猫(QOE2; SOR B)。此外，两项试验是针对实验室中对实验性致敏患猫进行评估，缺乏对自然发生哮喘患猫使用支气管扩张剂的研究。尽管如此，吸入式支气管扩张剂还是被推荐用于急性哮喘发作的管理和与吸入类固醇一起长期治疗猫哮喘(QOE3; SOR C)。显然，对于支气管扩张剂的疗效还需要进一步的研究。

H1-receptor blocking antihistamines

H1受体阻断型抗组胺药

Analysis of evidence

证据分析

There were seven open and uncontrolled studies reporting the efficacy of H1R-antihistamines in FASS; six were prospective and one was retrospective. One study was prospective, double-blinded and placebocontrolled. These included 164 cats: 37 treated with chlorphenamine/chlorpheniramine maleate (11 received concurrent omega three of six essential fatty acids),10 with clemastine fumarate, 20 with cyproheptadine hydrochloride,51 with cetirizine and 46 with loratidine. The outcome measures varied with the five prospective studies using owner-assessed pVAS (reductions of 0–25% poor, 26–50% fair, 51–75% good and 76– 100% excellent in four studies; and ≤25% mild, 25–50% moderate and ≥50% marked in one study). The retrospective study defined a “good” response as a marked reduction or resolution of clinical lesions and reduction or discontinuation of ongoing symptomatic medications, a “partial” as a reduction in clinical lesions with ongoing antipruritic drugs, and “no response” with no apparent change to lesions, pruritus and/or symptomatic medications. The cats presented with pruritus and a variety of the recognised reaction patterns associated with FASS. Most cats presented with more than one type of lesion. Seasonality was recorded for 99 cats, with 90 having perennial disease and nine seasonal disease. Two studies evaluated cetirizine and cyproheptadine in a model of feline asthma. Unfortunately, only two studies reported pharmacokinetic data of antihistamines in cats. Oral cyproheptadine was well-absorbed and had a half life of approximately 12 h. Cetirizine was well-absorbed after oral administration, with higher plasma concentrations than seen in humans and a half-life compatible with once-daily dosing.

有7项开放和不受控制的研究报告了H1R型抗组胺药对FASS的疗效，其中6例为前瞻性研究，1例为回顾性研究。其中一项研究是前瞻性、双盲和安慰剂对照研究。其中包括164只猫:37只使用扑尔敏/马来酸氯苯那敏(11只同时使用6种必需脂肪酸中的3种)，10只使用富马酸氯马斯汀，20只使用盐酸赛庚啶，51只使用西替利嗪，46只使用氯雷他定。5项采用宠主评估pVAS的前瞻性研究的结果不同(4项研究中pVAS降低范围0-25%较差、26-50%一般、51-75%良好、76-100%优秀;一项研究≤25%为轻度、25-50%为中度、≥50%为显著)。回顾性研究定义“良好”效果指临床病变明显减少或消除，对症治疗用药减少或停止,定义“部分”有效指临床病变减少，止痒药物持续使用,以及“无效”指病变、瘙痒表现和/或对症用药没有明显改变。这些猫表现出瘙痒和与FASS相关的各种已知的反应模式。大多数猫都有不止一种病变类型。99只猫记录有季节性，其中90只猫疾病为全年性，9只为季节性。两项研究评估了西替利嗪和赛庚啶在猫哮喘模型中的作用。不幸的是，只有两项研究报道了猫体内抗组胺药代动力学数据。口服赛庚啶吸收良好，半衰期约为12小时。口服西替利嗪吸收良好，其血浆浓度高于人，半衰期与每日一次剂量一致。

Analysis of efficacy

疗效分析

Treatment outcome data were available for 164 cats with FASS (see Table 8). Cats that responded to treatment were reported to do so within three to 10 days of starting treatment and to relapse within two to three days of stopping. There was no association between the responses to treatment and the type of lesions or seasonality.

可见164只FASS患猫治疗结果数据(见表8)。据报道，对治疗有反应的猫在开始治疗后3-10天内出现反应，停止治疗后2- 3天内复发。治疗反应与病变类型或季节性之间无相关性。

A retrospective study (QOE 3) reviewed type 1 antihistamine treatment in 31 cats. However, with the exception of cetirizine (n=19) and loratidine (n=18) (outcomes included in Table 6), specific treatments and outcomes were not reported. Most cats received more than one antihistamine with variable and inconsistent results. Overall, a good response was reported in two of 31, a partial response in 20 of 31, and a poor response in nine of 31 cats.

一项回顾性研究(QOE 3)回顾了31只猫的1型抗组胺药治疗。然而，除了西替利嗪(19只)和氯雷他定(18只)(结果包括在表6中)，没有报道特定的治疗和结果。大多数猫接受了一种以上的抗组胺药物治疗，结果不一致。总的来说，31只猫中有2只效果良好，20只部分有效，而31只猫中有9只效果不佳。

When used in a model of feline asthma, antihistamines such as cetirizine and cyproheptadine did not alter percentage of eosinophils in BALF, or serotonin and histamine concentrations in plasma or BALF.

当用于猫哮喘模型时，抗组胺药如西替利嗪和赛庚啶没有改变BALF中的嗜酸性细胞比例，或血浆或BALF中的血清素和组胺浓度。

Adverse effects

副作用

Most of the antihistamines were reported to be welltolerated. Adverse effects included sedation in two of 37 cats treated with chlorphenamine and diarrhoea in one of 10 cats given clemastine. However, adverse effects were reported in 11 of 20 cats treated with cyproheptadine; three cats were withdrawn from treatment (one with vomiting, two with polyphagia) and adverse effects were reported in another eight cats (vomiting in one, polyphagia in four and altered behaviour/vocalisation in four).

据报道，大多数抗组胺药的耐受性都很好。副作用包括37只接受扑尔敏治疗的猫中有2只镇静，10只接受氯马斯汀治疗的猫中有1只腹泻。然而，20只接受赛庚啶治疗的猫中有11只报告有副反应;3只猫退出治疗(1只呕吐，2只多食)，另外8只猫报告有副反应(1只呕吐，4只多食，4只行为/发声改变)。

Recommendations

建议

Oral antihistamines could provide a small and limited benefit in some cats with FASS and this is not likely to result in good-to-excellent response in most cases (QOE 2; SOR B). The available evidence supports the use of chlorphenamine as a first-line H1R-antihistamine (QOE 2; SOR B). The mode of action of these drugs in cats is unknown yet, based on recommendations in cAD, it is likely that they will be most effective in early and/or mild disease and when given proactively rather than reactively to manage an acute exacerbation (QOE3; SOR C). It is also possible that the sedative effect of first generation H1R-antihistamines may alleviate stress-associated triggers in FASS (QOE3; SOR C). The high frequency of adverse effects to cyproheptadine is of concern (QOE2; SOR B). There is no evidence supporting the use of antihistamines in cats with asthma (QOE2; SOR B).

口服抗组胺药对一些FASS患猫会有少数和有限的效果，但在大多数情况下，这并不可能产生良好至优秀的效果(QOE 2; SOR B)。现有证据支持扑尔敏作为一线H1R型抗组胺剂 (QOE 2; SOR B)。但这些药物在猫体内的作用模式尚不清楚，基于cAD的建议，它们很可能在早期和/或轻度疾病中最有效，作为急性发作期病例的主动治疗用药，而不是被动治疗 (QOE3; SOR C)。也有可能是一代H1R抗组胺药的镇静作用可能减轻FASS的应激相关触发因素(QOE3; SOR C)。赛庚啶的副反应频率高值得关注 (QOE2; SOR B)。没有证据支持对哮喘患猫使用抗组胺药物治疗(QOE2; SOR B)。

Essential fatty acids and palmitoylethanolamide

必需脂肪酸和十六酰胺乙醇

Analysis of evidence

证据分析

Treatment outcome data were available for 37 cats with FASS (see Table 9). In one prospective, double-blinded, placebo-controlled study 15 cats either received evening primrose oil (EPO) or olive oil as the placebo for 12 weeks. There was one prospective, double-blinded, placebo-controlled study evaluating 15 cats with FASS, two randomised studies with 11 and 14 atopic cats, one prospective study with 10 cats with FASS (and 18 cats with food allergy, flea bite hypersensitivity or miliary dermatitis, self-induced alopecia or eosinophilic granuloma without further diagnostic work-up) and 12 cats with miliary dermatitis, respectively. In another study, healthy cats were given essential fatty acids as a supplement to a standard diet. In some studies, cytological evaluation, fungal cultures, skin scrapings, flea control and elimination diets were performed as needed before inclusion to confirm the diagnosis of FASS. In others, cats showed clinical features of FASS, and differential diagnoses were not or not always evaluated. In three studies, only cats with miliary dermatitis (n=30) were included. In an open label study, 15 cats with nonfleaassociated FASS were given 10 mg/kg ultramicronised palmitoylethanolamide (PEAum) twice daily for 30 days. The outcome measures were a clinical assessment (pruritus, erythema, alopecia, and extent of eosinophilic plaques and granulomas) and evaluation of mast cell numbers in skin biopsies. One double-blinded, placebocontrolled randomised trial assessed the efficacy of PEAum in maintaining remission in cats with nonseasonal pruritus and FASS (described as nonflea-associated hypersensitivity dermatitis with a variety of reaction patterns). The cats initially were stabilised with two weeks of methylprednisolone (4–6 mg/cat/day) and then maintained on PEAum (n=21; approximately 15 mg/kg/day)or placebo (n=23) alone. The outcome was the time to relapse [≥2 point increase and/or score ≥ 4 in SCORFAD, ≥2 cm increase in pVAS or global assessment score of 3 (0–3 scale)]. One study assessed the preventive effects of omega-3 polyunsaturated fatty acids (omega3 PUFA) and luteolin supplementation on allergen-induced airway inflammation in eight A. suum-sensitised cats.

可见37只FASS患猫治疗结果数据(见表9)。在一项前瞻性、双盲、安慰剂对照研究中，15只猫分别服用月见草油(EPO)或橄榄油作为安慰剂，为期12周。有一个前瞻性,双盲,安慰剂对照研究评估15只FASS患猫,两个随机研究评估11只和14只特应性皮炎患猫,一个前瞻性研究评估10只FASS患猫(和18只食物过敏、跳蚤叮咬过敏症或粟粒性皮炎,自发性脱毛或嗜酸性肉芽肿,没有进一步诊断检查患猫)和12只粟粒性皮炎患猫。在另一项研究中，健康猫被喂食必需脂肪酸作为标准日粮的补充。在一些研究中，根据需要，在纳入前进行细胞学评估、真菌培养、皮肤刮片、跳蚤管理和食物排除试验，以确诊FASS。在另一些研究中，猫表现出FASS的临床特征，而鉴别诊断没有或不总是被评估。在三项研究中，只包括粟粒性皮炎患猫(30只)。在一项开放标签研究中，15只与跳蚤无关的FASS患猫被给予10 mg/kg超微粒十六酰胺乙醇(PEAum)，每天两次，连续30天。结果检测包括临床评估(瘙痒、红斑、脱毛、嗜酸性斑块和肉芽肿的范围)和在皮肤活组织检查中的肥大细胞数量的评估。一项双盲、安慰剂对照的随机试验评估了PEAum对患有非季节性瘙痒和FASS(描述为具有多种反应模式的与跳蚤无关的过敏性皮肤病)的猫维持缓解的疗效。最初，用甲基泼尼松龙稳定两周(4-6 mg/猫/天)，然后维持治疗单独使用PEAum (21只;大约15mg/kg/天)或安慰剂(23只)。复发时间结果是[SCORFAD评分增加≥2分和/或≥4分，pVAS增加≥2厘米或整体评估评分为3分(0-3分)]。一项研究评估了Ω3多不饱和脂肪酸(Ω3 PUFA)和木樨草素补充剂对8只对猪蛔虫过敏患猫的过敏原诱导的气道炎症的预防作用。

Analysis of efficacy

疗效分析

In one prospective, double-blinded, placebo-controlled study, 15 cats either received evening primrose oil (EPO) or olive oil as the placebo for 12 weeks. Mean pruritus, erythema, alopecia and overall scores did not improve significantly, nor was there a significant difference between groups. Two owners in each group considered their cats partially improved. In another randomised study, 11 cats received either EPO (n=6) or sunflower oil (n=5) for 12 weeks. Mean overall clinical, self-trauma and crusted papule scores decreased by >50% in both groups. In another study evaluating 14 cats with miliary dermatitis, seven of 14 showed good improvement after six weeks of 0.5 mL EPO/cat once daily. When combined with fish oil for another six weeks, 11 of 14 cats showed a good response (the “good response” was not further defined). When given fish oil for another six weeks without the EPO, clinical signs recurred in 10 of 11 cats. Five healthy cats and five cats with miliary dermatitis were administered an oil preparation with 33% omega 3 and omega 6 fatty acids in a ratio of 1:2, while five healthy cats and seven cats with miliary dermatitis were not treated. Serum concentrations of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) increased in the treated cats and the miliary dermatitis resolved in three of five affected cats. In a further study, healthy cats were given a fish oil (FO; EPA and DHA) or a flax seed oil [FSO; a-linolenic acid (ALNA, 18:3n-3)] supplement (n=14 in each group) to a standard diet (n-6:n-3 ratio 20:1) to achieve an n-6:n-3 ratio of 5:1. The supplements and diets were given for 12 weeks. Cutaneous reactions to histamine were reduced by 20–40% after FO and by 50% after FSO. FO raised leukotriene B (LTB) 5 levels and decreased the LTB4:LTB5 ratio; and FO and FSO decreased B, T-helper and total T-cell numbers, as well as proliferation to pokeweed mitogen. However, there was no effect on T-cytotoxic, natural killer and MHC class II cells, delayed type (type 4 cell-mediated) hypersensitivity, IL-2 expression or plasma IgG concentration, or concanavalin A or phytohaemagglutinin-triggered stimulation. No adverse effects were reported in any of these studies. In the uncontrolled trial of PEAum, pruritus/erythema/alopecia improved in 64.3% of the cats and eosinophilic dermatitis lesions in 66.7% (three of 15 completely resolved). There was no change in mast cell numbers, although their granularity increased. No adverse effects were noted. In the RCT assessing maintenance of methylprednisolone-induced remission of FASS, the mean time to relapse was significantly longer in the PEAum group (40.5 days; 13 of 19 cats relapsed) than the placebo group (22.2 days; 12 of 22 cats relapsed). Pruritus scores were significantly lower in the PEA-treated cats and there was no difference in lesion scores. Gastrointestinal effects were seen in four PEAum-treated cats (two withdrawn) and six placebotreated cats (one withdrawn).

在一项前瞻性、双盲、安慰剂对照研究中，15只猫分别接受月见草油(EPO)或橄榄油作为安慰剂，为期12周。平均瘙痒、红斑、脱毛和总评分没有显著改善，组间也没有显著差异。每组各有一位主人认为他们的猫得到了部分改善。在另一项随机研究中，11只猫接受EPO (6只)或葵花籽油(5只)为期12周。平均临床整体评估、自发性创伤和结痂性丘疹评分均下降＞50%。在另一项对14只患有粟粒性皮炎的猫进行评估的研究中，14只猫中的7只在每天服用0.5毫升EPO 6周后表现出良好的改善。再与鱼油混合6周后，14只猫中有11只表现出良好的反应(良好反应没有进一步定义)。在没有给EPO的情况下，再给11只猫中有10只服用鱼油6周后，临床症状又出现了。将5只健康猫和5只患有粟粒性皮炎的猫按1:2的比例给予含有33% omega 3和omega 6脂肪酸的油制剂，而5只健康猫和7只患有粟粒性皮炎的猫没有接受治疗。治疗后的猫血清中二十碳五烯酸(EPA, 20:5n-3)和二十二碳六烯酸(DHA, 22:6n-3)的浓度增加，5只患猫中有3只的粟粒性皮炎消退。在进一步的研究中，给健康的猫吃鱼油(FO;EPA和DHA)或亚麻籽油[FSO;在标准饲粮(n-6:n-3比例20:1)中添加a-亚麻酸(ALNA, 18:3n-3)，每组14只，使n-6:n-3比例达到5:1。这些补充剂和日粮持续给12周。皮肤对组胺的反应在FO组和FSO组分别降低了20-40%和50%。FO升高白三烯B (LTB) 5水平，降低LTB4:LTB5比值，FO和FSO降低了B、T辅助细胞和T细胞总数，以及对商陆有丝分裂原的增殖。然而，对T细胞毒性、自然杀伤细胞和MHC II类细胞、延迟型(4型细胞介导的)超敏反应、IL-2表达或血浆IgG浓度、伴菜青素A或植物血凝素触发的刺激均无影响。在这些研究中没有任何副反应的报道。在PEAum的非控制试验中，64.3%患猫的瘙痒/红斑/脱毛改善，嗜酸性皮炎病变改善了66.7%(15例中的3例完全解决)。肥大细胞的数量没有变化，但它们的颗粒度增加。未发现副反应。在评估甲基泼尼松龙诱导的FASS缓解维持情况的RCT中，PEAum组的平均复发时间明显更长(40.5天;19只猫中有13只复发)比安慰剂组(22.2天;22只猫中有12只复发)。用PEA治疗的猫瘙痒评分明显较低，而病变评分没有差异。4只服用了PEA的猫(2只停用)和6只服用安慰剂的猫(1只停用)出现了胃肠道效应。

When eight asthmatic cats sensitised to A. suum received four weeks of omega-3 fatty acids (20 mg once daily) and luteolin (10 mg once daily), analysis of BALF total and differential cell counts did not reveal any significant differences between treated and untreated A. suum-stimulated cats. However, concentrations of leukotriene A4 increased and airway responsiveness decreased after the supplement intake.

当8只哮喘猫对猪蛔虫过敏时，它们接受了4周Ω-3脂肪酸(每天20mg)和木樨草素(每天10mg)，BALF总量和不同细胞计数的分析并没有显示任何显著的差异，治疗和未治疗的猪蛔虫过敏猫。然而，摄入量补充后白三烯A4浓度增加，气道反应性下降。

Recommendations

建议

Based on available data, there is limited evidence for moderate efficacy of EFA supplementation in cats with miliary dermatitis (QOE2; SOR B). A single study in healthy cats showed decreased reactivity to histamine with variable and moderate suppression of B- and T-cell function. However, the clinical relevance of these findings remains unknown. There is moderate evidence of moderate efficacy for PEAum in FASS (QOE2; SOR B). There is insufficient evidence for the benefit of EFAs or PEAum in feline asthma.

基于现有的数据，有限的证据表明补充EFA对患有粟粒性皮炎的猫中度有疗(QOE2; SOR B)。一项对健康猫的单一研究显示，对组胺的反应降低，B细胞和T细胞的功能受到不同程度和中度的抑制。然而，这些发现的临床意义仍然未知。有中度证据表明，PEAum对FASS中度有效(QOE2; SOR B)。没有足够的证据证明EFAs或PEAum对猫哮喘有好处。

Maropitant

马罗皮坦

Analysis of evidence

证据分析

One open study evaluated maropitant at 2 mg/kg orally once daily for four weeks as treatment for cats with FASS. Two randomised, placebo-controlled studies looked at the effect of maropitant on acute and chronic asthma, respectively, in experimentally sensitised cats.

一项开放研究评估了口服马罗匹坦为以2mg/kg，每天一次，为期四周，作为治疗FASS患猫。两项随机的、安慰剂对照的研究分别在实验室致敏患猫上观察了马罗匹坦对急性和慢性哮喘的影响。

Analysis of efficacy

疗效分析

Maropitant decreased SCORFAD from 7.8 to 2.2 and pruritus scores from 7.1 to 2.3, respectively, in 12 cats with FASS. Ten of those cats improved by >50% in lesions, and 11 of 12 by >50% in pruritus.

在12只FASS患猫中，马罗匹坦将SCORFAD评分从7.8降低到2.2，瘙痒评分从7.1降低到2.3。10只猫的皮肤病变改善了50%，12只猫中的11只瘙痒改善了50%。

When administered to artificially sensitised cats with feline asthma at 2 mg/kg subcutaneously immediately after allergen challenge, maropitant did not diminish clinical scores or airway eosinophilia. Likewise, there was no difference in clinical scores or airway eosinophilia when sensitised cats were administered maropitant at 2 mg/kg every 48 h for four weeks, although daily administration was not evaluated.

当在过敏原激发后立即给人为致敏猫哮喘患猫皮下注射2mg/kg马罗匹坦时，不会降低临床评分或气道嗜酸性细胞。同样，当致敏患猫每48小时给马罗皮坦2mg/kg，持续四周时，临床评分或气道嗜酸性细胞数没有差异，但没有对每日给药进行评估。

Adverse effects

副作用

Increased salivation immediately after maropitant administration occured in two of 12 cats with FASS.

在12只FASS患猫中，有2只在给药后立即出现流涎增加。

Recommendations

建议

There is limited evidence of good efficacy for maropitant in FASS (QOE2; SOR B). There is currently no evidence supporting the use of maropitant in cats with asthma (QOE1; SOR A).

有限的证据表明马罗匹坦在FASS中有良好的疗效 (QOE2; SOR B)。目前没有证据支持对哮喘患猫使用马罗皮坦的有效性(QOE1; SOR A)。

Antibiotics

抗生素

Analysis of evidence

证据分析

There was one double-blinded, placebo-controlled study on the efficacy of oral amoxicillin-clavulanate[Clavamox; Pfizer Animal Health (now Zoetis): Madison, NJ, USA] on eosinophilic plaques (amoxicillin-clavulanate 12–14.6 mg/kg twice daily, n=4; placebo, n=5) and indolent ulcers (amoxicillin-clavulanate 12– 16.2 mg/kg twice daily, n=4; placebo, n=4). All of the cats had cytological evidence of infection with neutrophils and intracellular bacteria at entry. The cats were treated for three weeks with no other treatment apart from flea control. No adverse reactions were reported. Another study evaluated the influence of doxycycline (5 mg/kg twice daily) on cats with experimentally induced asthma.

有一项关于口服阿莫西林-克拉维酸[Clavamox; Pfizer Animal Health (now Zoetis): Madison, NJ, USA]对嗜酸性斑块(阿莫西林-克拉维酸12-14.6mg/kg，每日两次，n=4；安慰剂，n=5)和无痛性溃疡(阿莫西林克拉维酸12-16.2mg/kg，每日2次，n=4；安慰剂，n=5)的有效性研究。所有的猫在入选时都有细胞学支持感染的证据，即可见中性粒细胞和胞内菌。这些猫被治疗了3周，除跳蚤管理外没有其他治疗。无副反应报告。另一项研究评估了多西环素(5mg/kg，每日两次)对实验性哮喘患猫的影响。

Analysis of efficacy

疗效分析

Treatment with amoxicillin-clavulanate significantly reduced the mean lesion size of the eosinophilic plaques by 96% and indolent ulcers by 43% compared to the placebo (0% and 37% increases, respectively). There also was a decrease in the number of highpower microscope fields with cytological evidence of infection of 80% in the eosinophilic plaque group and 65% in the indolent ulcer group compared to placebo (16% decrease and 13% increase, respectively). It needs to be pointed out that eosinophilic plaques, indolent ulcers and linear granulomas are reaction patterns associated with other underlying allergic and nonallergic causes, and those cats were diagnosed with secondary bacterial infections. In cats with asthma, four days of doxycycline did not influence the early or late asthmatic response.

与安慰剂组相比，阿莫西林-克拉维酸治疗嗜酸性斑块组的平均病变大小显著减少96%，无痛性溃疡组的平均病变大小显著减少43%(分别增加0%和37%)。高倍镜下，感染的细胞学证据也有减少，与安慰剂组相比，嗜酸性斑块组降低80%，无痛性溃疡组降低65%(分别减少16%和增加13%)。需要指出的是，嗜酸性斑块、无痛性溃疡和线性肉芽肿是与其他潜在的过敏和非过敏病因相关的反应模式，这些猫被诊断为继发性细菌感染。在哮喘猫中，4天的多西环素没有影响早期或晚期的哮喘反应。

Recommendations

建议

The small and well-conducted study in FASS provided evidence of high efficacy of amoxicillin-clavulanate in eosinophilic plaques and indolent ulcers (QOE 1, SOR A). However, it is unclear whether the improvement was the result of eliminating the bacteria from the lesions and/or immunomodulation, and whether treatment resulted in a sustained response. In addition, current antimicrobial treatment guidelines for skin infections (summarised in Brissot, 2016) emphasise using topical antimicrobial therapy over systemic treatment and, where this is necessary, using the lowest tier, most narrow-spectrum drug possible for the shortest time required to clear the infection. Long-term therapy in the absence of a bacterial infection usually is discouraged, and veterinarians are advised to follow antimicrobial treatment guidelines established in their country of practice and/or in international consensus recommendations. So far, no evidence has been published supporting the use of antibiotics in feline asthma (QOE 2, SOR B).

FASS的小规模管理良好的研究提供了阿莫西林克拉维酸钾对嗜酸性斑块和无痛性溃疡的高有效性(QOE 1, SOR A)。然而,目前尚不清楚改善是否是与病变的细菌消除和/或免疫调节有关,以及是否治疗会持续有效。此外，目前针对皮肤感染的抗菌治疗指南(2016年的布里索总结)强调外部抗菌治疗优于全身治疗，必要时，在最短时间内使用最低级、最窄谱的药物清除感染。通常不鼓励在没有细菌感染的情况下进行长期治疗，建议兽医遵循其所在国和/或国际共识建议制定的抗生素治疗指南。到目前为止，没有发表的证据支持在猫哮喘中使用抗生素有效(QOE 2, SOR B)。

Inhaled lidocaine.

吸入利多卡因

Analysis of evidence

证据分析

Nebulised lidocaine has received interest as a corticosteroid-sparing drug in human asthmatics, reducing airway resistance and peripheral blood eosinophilia. It was evaluated in healthy and experimentally asthmatic cats in a cross-over study. Five healthy and nine experimentally asthmatic cats received nebulised lidocaine at the dose of 2 mg/kg three times a day for two weeks in a cross-over design.

雾化利多卡因作为一种节省糖皮质激素的药物在人医哮喘患者中引起了人们的兴趣，它可以减少气道阻力和外周血嗜酸性细胞增多。对健康和实验室诱发哮喘患猫进行交叉研究。在交叉设计中，5只健康的和9只实验室诱发哮喘猫接受了每天3次、每次2mg/kg的利多卡因雾化吸入，持续2周。

Analysis of efficacy

疗效分析

In healthy cats, lidocaine did not significantly alter BALF eosinophilia or the concentration of methacholine increasing baseline airway resistance by 200%. There was no difference in eosinophil percentages in the BALF in asthmatic cats treated with lidocaine (36±10%) or placebo (33±6%). However, lidocaine significantly increased the concentration of methacholine increasing baseline airway resistance by 200% compared with placebo (10±2 versus 5±1 mg/mL). Adverse effects were not seen with nebulized lidocaine.

在健康猫中，利多卡因没有显著改变BALF嗜酸性细胞增多或甲胆碱浓度使基线气道阻力增加200%。利多卡因(36±10%)和安慰剂(33±6%)治疗哮喘患猫的BALF中的嗜酸性细胞比例没有差异。然而，与安慰剂相比，利多卡因显著增加了甲胆碱浓度，增加了200%的基线气道阻力(10±2 vs 5±1mg/mL)。利多卡因雾化未见副反应。

Recommendations

建议

Based on this one study, lidocaine may serve as adjunctive therapy in feline asthmatics with mild beneficial effects on airflow obstruction (QOE2; SOR B).

基于这项研究，利多卡因可以作为猫哮喘辅助治疗，对气流阻塞有轻微的有益作用(QOE2; SOR B)。

Mesenchymal stem cell therapy

间充质干细胞治疗

Analysis of evidence

证据分析

Adipose-derived mesenchymal stem cells (MSC) were evaluated in a small RCT in an experimental feline asthma model. In this pilot study, allogenic adipose-derived MSCs were administered in five intravenous infusions at D0, D14, D28, D98 and D130 to four of six cats experimentally sensitized with Bermuda grass while two cats were treated with placebo. BALF eosinophilia was evaluated at seven time points over nine months, along with blood samples to evaluate T-lymphocyte phenotype, total Bermuda grass allergen-specific lymphocyte proliferation, IL-10 production from lipopolysaccharide (LPS)-stimulated whole blood, and numbers of IL-10-producing cells. Additionally, thoracic computed tomography (CT) in conjunction with abbreviated pulmonary function testing was compared to that of healthy cats used as controls.

脂肪来源的间充质干细胞(MSC)在一个小的随机对照试验中对实验室诱发猫哮喘模型进行评估。在这项初步研究中，在第0、14、28、98和130天，5次静脉注射异源脂肪来源的间充质干细胞给6只实验室用百慕大草致敏的猫中的4只，另外2只接受安慰剂治疗。研究人员在9个月的7个时间点对BALF嗜酸性细胞增多症进行了评估，并对血液样本进行了评估，以评估T淋巴细胞表型、总百慕大草过敏原特异性淋巴细胞增殖、由脂多糖(LPS)刺激的全血产生IL-10，以及IL-10产生细胞的数量。此外，将胸部计算机断层扫描(CT)结合简化肺功能测试与健康猫作为对照组进行比较。

Analysis of efficacy

疗效分析

Diminished airway hyper-responsiveness was noted in all MSC-treated compared with the placebo-treated cats at D133. Lung attenuation and bronchial wall-thickening scores consistent with decreased airway remodelling were significantly reduced in MSC-treated versus untreated asthmatic cats.

在第133天，所有MSC治疗的猫与安慰剂治疗的猫相比，气道高反应性降低。与未治疗的哮喘猫相比，接受MSC治疗的哮喘猫肺衰减和支气管壁增厚评分与气道重塑减少一致。

Recommendations

建议

There is limited evidence of mild-to-moderate long-term efficacy of MSC in the treatment of feline asthma (QOE2; SOR B).

有限的证据表明MSC在治疗猫哮喘方面有轻度到中度的长期有效性 (QOE2; SOR B)。

2heiyanquan

18981110357

红蓝紫

笼中红细胞

南海

笼中红细胞

秘鸢

袁丽娟

廊坊永鑫罗玄

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