猫哮喘

爱喵喵

Feline Asthma

Laura A. Nafe, DVM, MS, DACVIM (SAIM), University of Missouri

RESPIRATORY MEDICINE（呼吸内科）

JULY 2020 翻译：寇明明、何珊。校对：石慧

Feline asthma is a lower airway disease that affects 1% to 5% of cats,1 most commonly young to middle-aged cats.1 Although median age on diagnosis has been reported to be 4 to 5 years, most cats with asthma experience clinical signs earlier in life.1 Classified as an allergic disease, feline asthma is the result of a type-1 hypersensitivity to specific aeroallergens.2 This immune response results in cytokine release and elaboration that can ultimately cause pathologic airway changes.

猫哮喘是一种下呼吸道疾病，有1% to 5%的猫患病，最常见于年轻至中年猫。尽管据报道诊断时中位年龄是4-5岁，大部分哮喘猫在更早的时候就有临床症状了。猫哮喘被归类为过敏性疾病，是对某些空气过敏原产生的1型超敏反应。这个免疫反应导致细胞因子释放和炎症，最终可导致呼吸道出现病理性变化。

Hallmark clinical features of asthma include bronchoconstriction, airway edema, airway eosinophilia, and excessive mucus production. The combination of these features can result in cough, tachypnea, and/or expiratory dyspnea.1,3 Compounding airway edema, smooth muscle bronchoconstriction, and mucus hypersecretion can result in airflow limitation, which can be at least partially reversible with bronchodilator therapy. If left untreated, chronic airway inflammation can result in irreversible airway remodeling.

哮喘的临床特征包括支气管收缩、气道水肿、气道嗜酸性粒细胞增多和黏液大量产生。这些组合在一起可以导致咳嗽、呼吸急促和/或呼气困难。在气道水肿的基础上，支气管平滑肌收缩和黏液过度分泌可导致气流受限，对此使用支气管扩张剂至少可部分逆转。如果不治疗，慢性气道炎症可能导致无法逆转的气道重塑。

Clinical Signs临床症状

Clinical signs associated with feline asthma include cough, tachypnea, open-mouth breathing, and/or respiratory distress, typically characterized by a prolonged expiratory phase of respiration and abdominal push. Some patients may have only one of these clinical signs, whereas others may have both a chronic cough and intermittent exacerbations resulting in respiratory distress with expiratory effort.3 Accordingly, clinical signs can be episodic and vary in severity, from a mild, intermittent cough to life-threatening dyspnea (ie, status asthmaticus). Pet owners may struggle to identify a true cough and may be confused with “vomiting hairballs” without production of a hairball.

猫哮喘的临床症状包括咳嗽、呼吸急促、张口呼吸或/和呼吸窘迫，典型的特征是呼吸的呼气阶段延长和腹部用力呼气。有些患猫可能只有这些症状中的一个，然而其他猫可能同时有慢性咳嗽和间歇性恶化导致呼吸窘迫伴有呼气用力。因此，临床症状可能是阵发性的，严重程度各不相同，从轻度间歇性咳嗽到危及生命的呼吸困难（即哮喘持续状态）。宠物主人可能难以识别真正的咳嗽，并且可能会与没有吐出来毛球的“吐毛球”混淆。

Diagnosis诊断

Definitive diagnosis of feline asthma can be challenging due to clinical features that overlap with various other cardiopulmonary conditions, including chronic bronchitis, heartworm-associated respiratory disease, and pulmonary parasitic disease. Diagnosis can be facilitated through a combination of consistent historical information, clinical signs (ie, cough and/or respiratory distress), physical examination, laboratory data (eg, CBC, serum chemistry profile, fecal flotation and analysis, urinalysis, heartworm antigen and antibody testing), imaging (eg, thoracic radiography, thoracic ultrasonography, CT, bronchoscopy, echocardiography), airway sampling, and additional diagnostic testing (eg, airway cytology) to rule out other causes of eosinophilic airway inflammation.

确诊猫哮喘可能具有挑战性，因为临床症状跟许多其他的心肺疾病重叠，包括慢性支气管炎，心丝虫引起的呼吸系统疾病，和肺部寄生虫疾病。诊断需要根据相符的病史，临床症状（如咳嗽和/或呼吸窘迫），体格检查，实验室数据（如CBC，血清生化指标，粪便漂浮和检查，尿液分析，心丝虫抗原和抗体检查），影像（如胸部X光片，胸部超声，CT，支气管镜检查法，心超），气道采样，和其他检查（如气道细胞学）来排除其他导致嗜酸性粒细胞性气道炎症的原因。

Physical examination may be normal or may reveal tachypnea, inducible cough on tracheal palpation, and/or abnormalities on thoracic auscultation (eg, increased bronchovesicular sounds, expiratory wheezes). Classic radiographic findings include a diffuse bronchial or bronchointerstitial pattern, hyperinflation due to air trapping, and/or collapse of the right middle lung lobe due to mucus plug obstruction (Figure 1).3,4 Because ≈20% of asthmatic cats have normal thoracic radiographs, asthma should remain on the differential list for any cat with respiratory distress and normal thoracic radiographs.5 In addition, a bronchial or bronchointerstitial pattern is also the predominant pulmonary pattern seen in cats with chronic bronchitis and/or heartworm-associated respiratory disease, making it challenging to differentiate these conditions from asthma via only physical examination and radiography.

体格检查可能正常或发现呼吸急促，气管触诊诱发咳嗽，有/无胸部听诊异常（如支气肺泡音增强，呼气哮鸣音）。典型X光片发现包括弥散性支气管型或支气管间质型，空气潴留引起的过度充气，和/或黏液栓子阻塞导致的肺右中叶塌陷（图 1）。因为大约20%哮喘猫的胸部X光片是正常的，所以任何呼吸窘迫但胸片正常的猫的鉴别诊断列表仍应包括哮喘。此外，支气管型或支气管间质型也是患慢性支气管炎或心丝虫相关呼吸系统疾病的猫的主要肺型，因此只依靠体格检查和X光片来区分这些疾病和哮喘具有挑战性。

 

FIGURE 1 Ventrodorsal thoracic radiograph of an asthmatic cat demonstrating a diffuse bronchial pattern and collapse of the right middle lung lobe, which developed secondary to mucus accumulation and resulted in atelectasis

图1一只哮喘猫的腹背位胸片显示弥散性支气管型和右中肺叶塌陷，肺塌陷继发于黏液聚集，导致肺不张。

Bronchoscopy may be used in asthmatic cats to evaluate airway structure and collect bronchoalveolar lavage fluid (BALF) for cytology, culture and susceptibility testing, and Mycoplasma spp PCR testing. Alternatively, blind bronchoalveolar lavage may also be performed in cats that show diffuse radiographic changes. Clinicians should be cautious when interpreting BALF culture and Mycoplasma spp PCR results in combination with BALF cytology results, as airways (especially the trachea) are not sterile and the presence of bacteria or Mycoplasma spp does not equate to active infection.6

支气管镜检查可用于哮喘猫来评估气道结构和收集支气管肺泡灌洗液（BAL），用于细胞学、培养和药敏，以及支原体PCR检测。另外，对于X光片上有弥漫性变化的猫，也可以进行盲法支气管肺泡灌洗。临床医生判读支气管肺泡灌洗液培养结果和支原体PCR结果时，应结合支气管肺泡灌洗液细胞学检查结果，因为气道（尤其是气管）不是无菌的，因此存在细菌或支原体并不等同于感染。

Bronchoscopy findings are often nonspecific in asthmatic patients and may include excessive mucus accumulation, airway hyperemia, and/or epithelial irregularities.1 Eosinophilic airway inflammation is characteristic of but not specific to asthma (Figure 2), as parasitic disease commonly results in airway eosinophilia. Historically, eosinophilic airway inflammation has been defined as >17% eosinophils present in BALF; however, recent evidence suggests that >5% eosinophils is considered abnormal in feline BALF.7,8 Clinicians should evaluate BALF eosinophil percentage in light of clinical signs and concurrent conditions associated with eosinophilia (eg, allergic skin disease). Most asthmatic cats typically have significant BALF eosinophilia; some can have lower eosinophil and higher neutrophil numbers, particularly in chronic asthma cases. A heartworm antigen and antibody test, fecal flotation, and Baermann test should be performed in all cases. In addition, the author commonly institutes empiric antiparasitic treatment, even if results are negative.

哮喘猫的支气管镜检查结果经常没有特异性，可能包括大量黏液聚集、气道充血和/或上皮不规则。嗜酸性气道炎症是哮喘的特征（图2），但不是哮喘特有的，因为寄生虫性疾病经常导致气道嗜酸性粒细胞增多。传统上，嗜酸性气道炎症的定义是支气管肺泡灌洗液中嗜酸性粒细胞＞17%；然而，最近的证据表明，猫支气管肺泡灌洗液中嗜酸性粒细胞>5%即为异常。临床医生应结合临床症状和其他导致嗜酸性粒细胞增多的疾病（如过敏性皮肤病），来评估支气管肺泡灌洗液中嗜酸性粒细胞的百分比。大多数哮喘猫的支气管肺泡灌洗液中有大量的嗜酸性粒细胞；有些猫的嗜酸性粒细胞数量较低但中性粒细胞数量更高，特别是在慢性哮喘病例中。所有病例均应进行心丝虫抗原和抗体检测、粪便漂浮和贝尔曼检测。此外，即使结果为阴性，作者也会经常进行经验性抗寄生虫治疗，。

 

FIGURE 2 BALF cytology from a cat demonstrating a predominance of eosinophils (arrows), which is characteristic of feline asthma. Image courtesy of Dr. Susan Fielder, Oklahoma State University。

图2 一只猫的支气管肺泡灌洗液细胞学显示以嗜酸性粒细胞（箭头）为主，这是猫哮喘的典型特征。图片感谢Dr. Susan Fielder, Oklahoma State University。

Treatment & Management

治疗和管理

Management of feline asthma consists of both acute and chronic treatment strategies. Clinicians and owners should understand that asthma is not a condition that can be cured; lifelong environmental and medical management are necessary.

猫哮喘的管理包括急性和慢性治疗方法。临床医生和主人应该明白，哮喘不是一个可以治愈的疾病；终身的环境和药物管理是必要的。

Cats presented in status asthmaticus require acute management consisting of supplemental oxygen, stress reduction and minimal handling, and bronchodilator therapy (eg, inhaled albuterol [via metered dose inhaler], injectable terbutaline). In the author’s clinical experience, injectable terbutaline is preferred over inhaled albuterol in the emergency setting, as cats in respiratory distress typically may not inspire deeply enough to appropriately deliver inhaled medication to the lower airways. Identifying an expiratory respiratory pattern can be suggestive of bronchoconstriction and may lead the clinician to implement early intervention with bronchodilator therapy.Expiratory respiratory patterns are characterized by an abdominal push during exhalation. If an obvious expiratory pattern is not identified, evaluation for other causes of respiratory distress (eg, pleural effusion, congestive heart failure) should be performed prior to empiric treatment with a bronchodilator.Clinicians should evaluate patients for a heart murmur or gallop rhythm and perform cage-side thoracic ultrasonography to assess for pleural effusion and/or pulmonary edema (eg, presence of B lines). If other causes of respiratory distress are not evident on initial evaluation, intervention with a bronchodilator for possible asthma may be warranted.

处于持续哮喘发作的猫需要急性管理，包括供氧、减少压力、最小化保定、支气管扩张剂（例如计量式沙丁胺醇吸入剂、注射特布他林）。在作者的临床经验中，急诊时注射特布他林优先于吸入沙丁胺醇，因为猫呼吸困难时可能吸气不够深，无法将药物输送到下气道。确认呼气困难可提示支气管收缩，继而引导临床医生尽早使用支气管扩张剂来干预。呼气困难的特点是呼气时腹部用力前推。如果没有发现明显的呼气困难，在经验性使用支气管扩张剂治疗之前，应该先评估呼吸困难的其它原因（如胸腔积液、淤血性心衰）。临床医生应评估猫是否有心杂音或奔马律，并做笼旁胸腔超声来评估是否有胸腔积液和/或肺水肿（如存在B线）。如果初始检查未发现其他导致呼吸困难的原因，用支气管扩张剂治疗可能的哮喘是合理的。

Management of chronic feline asthma is aimed at reducing airway inflammation and preventing or reducing airflow-limiting bronchoconstriction.1 Reduced inflammation is best achieved by minimizing exposure to aeroallergens and environmental irritants (eg, aerosols, dust) and administration of oral glucocorticoids (eg, prednisolone).Minimizing environmental allergens is best achieved by reducing exposure to known allergens (eg, eliminating outdoor access), cleaning bedding and other surfaces in the household frequented by the cat, and using an air filter to improve air quality.Oral glucocorticoid (prednisolone) therapy should be initiated at a dose of 1-2 mg/kg/day.The dose may be tapered by 25% to 50% every 2 to 4 weeks depending on clinical response. The goal is to taper steroids to the lowest effective dose.

猫慢性哮喘的治疗目标是减少气道炎症和预防或减少限制气流的支气管收缩。减少炎症最有效的措施是尽量减少接触气源性过敏原和环境刺激（如气溶胶、灰尘），以及口服糖皮质激素（如泼尼松龙）。减少环境过敏原最好的方式是避免接触各种已知过敏原（如禁止外出），经常清洁猫使用的床上用品和家里其它表面，以及使用空气净化器提高空气质量。口服糖皮质激素（泼尼松龙）的最初剂量应为1-2mg/kg/天。根据临床反应，每2-4周可减少剂量的25-50%。目标是逐渐减少类固醇到最低有效剂量。

Inhalant Therapy吸入疗法

Some cats can be transitioned to receiving only inhaled steroid therapy (eg, fluticasone) to minimize the systemic adverse effects of oral glucocorticoids and maintained on inhaled glucocorticoids alone for long-term management.It is important to overlap the inhaled steroid with oral glucocorticoid therapy, as it is believed that inhaled glucocorticoids require ≈2 weeks to achieve full clinical effect.Although the author frequently initiates inhaled fluticasone at a dose of 110 μg every 12 hours, a study evaluating inhaled fluticasone in cats with experimentally induced asthma found that airway eosinophilia was controlled with a variety of doses, including 44 μg, 110 μg, and 220 μg, administered every 12 hours.The efficacy of lower-dose fluticasone has not been evaluated in cats with naturally occurring asthma.In cats with concurrent conditions in which systemic glucocorticoids are contraindicated (eg, congestive heart failure, diabetes mellitus), inhaled glucocorticoid therapy and/or oral cyclosporine may be considered.

一些猫可以转变为仅用吸入类固醇（如氟替卡松）,以最大限度地减少口服糖皮质激素的全身不良反应，并且可以仅用吸入糖皮质激素长期管理。使用吸入类固醇时，非常重要的是需要和口服糖皮质激素联用一段时间，因为一般认为吸入性糖皮质激素需要大约2周才能达到最大临床效果。尽管笔者给猫使用吸入氟替卡松时的起始剂量经常是每12小时110μg，一项评估吸入氟替卡松治疗实验性诱发的猫哮喘的研究发现，不同剂量均可控制气道嗜酸性粒细胞增多症，包括每12小时44μg、110μg和220μg。但是对于自然患哮喘的猫，低剂量氟替卡松的效果尚未被评估。

对于有并存病且全身性糖皮质激素是禁忌（如淤血性心力衰竭和糖尿病）的猫，可以考虑吸入性糖皮质激素和/或口服环孢素

Bronchodilator Therapy支气管扩张剂治疗

Chronic bronchodilator therapy is not necessary in all cats with asthma and is only recommended in patients that have signs associated with bronchoconstriction (eg, respiratory distress, episodic tachypnea). Inhaled racemic albuterol should not be used for chronic management of bronchoconstriction due to the proinflammatory effects of the S-enantiomer; however, racemic albuterol can be used at home by owners for rescue as needed.11 Oral terbutaline or theophylline may also be used for chronic bronchodilator therapy. Although many patients may need bronchodilator therapy initially, once airway inflammation is controlled with glucocorticoid therapy, many can be weaned off bronchodilators long-term and managed as needed. In addition, feline asthma should never be managed with bronchodilator therapy alone, as bronchodilators will not address airway inflammation, which is an integral component of controlling asthma.

长期支气管扩张剂治疗对哮喘猫来说不都是必要的，仅建议用于有支气管收缩的症状的猫(如呼吸困难和阵发性呼吸急促)。沙丁胺醇消旋体吸入剂不应长期使用来控制支气管收缩，因为其中的左旋体有促炎作用；然而，根据需要主人可在家使用沙丁胺醇消旋体用于急救。口服特布他林或茶碱也可长期使用来扩张支气管。尽管许多猫最开始需要支气管扩张剂，在糖皮质激素控制住气道炎症之后，许多猫可以停用支气管扩张剂，而只在需要时使用。除此之外，一定不能单独使用支气管扩张剂来管理猫哮喘，因为支气管扩张剂不能治疗气道炎症，而抑制炎症是控制哮喘必不可少的部分。

Additional Therapeutic Options其它治疗选择

Various other therapeutic drugs (ie, cyproheptadine, cetirizine, nebulized lidocaine, maropitant) have been investigated for management of experimentally induced asthma in cats12-14; although some show promise in reducing airflow limitation, none have been shown to be effective as monotherapy for management of feline asthma. As a result, these other therapeutics can be considered as adjunctive treatments along with glucocorticoids. Immunotherapy and mesenchymal stem cell therapy have shown promise as future novel therapeutics and warrant further investigation both in cats that have experimental and naturally occurring asthma.

研究有报道使用许多其他药物（如赛庚啶、西替利嗪、吸入性利多卡因、马罗匹坦）来治疗实验性诱发的猫哮喘；尽管一些药物显示可以降低气流限制，但没有哪种单一药物足以管理猫哮喘。因此，这些其他药物可以考虑作为糖皮质激素的辅助疗法。免疫疗法和间质干细胞疗法已经显示有希望作为未来新疗法，值得在猫的实验性和自然发生的哮喘中进一步研究。

Prognosis & Prevention预后和预防

Prognosis for feline asthma is typically good with prompt diagnosis and appropriate management. Status asthmaticus, however, is a potentially life-threatening manifestation of asthma in cats, especially if not recognized and treated appropriately in the emergency setting. Prevention is challenging, as it is impossible to truly prevent the onset of an allergic condition like asthma. Prevention and/or reduction of clinical signs can be achieved through avoidance of known aeroallergens.

如果能够及时诊断和正确管理，猫哮喘的预后一般很好。然而，哮喘持续状态是猫哮喘的一个潜在威胁生命的表现，特别是在急诊时没有正确识别和治疗的话。预防具有挑战性，因为不可能真正地预防像哮喘这种过敏性疾病的发作。可以通过避免已知过敏原来预防和/或减少临床症状。

Clinical Follow-Up & Monitoring临床随访和监测

Follow-up evaluation is necessary for successful chronic management of cats with asthma. Clinicians should decide whether to reduce a steroid dose based on clinical signs, physical examination, thoracic radiography, and, occasionally, resolution of airway eosinophilia. Long-term management of feline asthma is aimed at lowering glucocorticoid doses to the lowest effective dose that controls clinical signs and airway inflammation. Some patients may be transitioned to inhaled glucocorticoid therapy (eg, fluticasone) using a space chamber to aid drug delivery. Patients started on bronchodilator therapy can often be tapered off once airway inflammation is controlled.

跟踪评估对成功长期管理猫哮喘来说是必要的。临床医生应该根据临床症状、体格检查、胸腔影像学、偶尔气道嗜酸性粒细胞增多症的改善情况，来决定是否要减少类固醇剂量。猫哮喘的长期管理目标是减少糖皮质激素的剂量至可以控制临床症状和气道炎症的最低有效剂量。一些猫可以转为吸入性糖皮质激素疗法（如氟替卡松），使用空气桶（如空气猫）帮助药物吸入。一旦气道炎症得到控制，可以逐渐减少至停用之前就开始用的支气管扩张剂。

Feline asthma patients are generally responsive to treatment with a glucocorticoid ± bronchodilator. In feline respiratory patients unresponsive to standard asthma therapy, the diagnosis should be reconsidered and further diagnostics pursued.

哮喘猫咪通常对糖皮质激素 ±支气管扩张剂有效。若有呼吸道疾病的猫咪对标准的哮喘治疗没有反应，结果需要重新考虑，并且进一步诊断。

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