ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Asthma and COPD overlap (ACO)

Asthma and COPD overlap (ACO)
Literature review current through: Jan 2024.
This topic last updated: Aug 08, 2023.

INTRODUCTION — Asthma and chronic obstructive pulmonary disease (COPD) have characteristic clinical features, but patients with clinical features of both asthma and COPD are often encountered in clinical practice. This observation has led to the introduction of the term "asthma-COPD overlap" (ACO), which is a description of a collection of clinical features rather than a definition of a single entity [1,2]. While ACO is likely not a single disease, nor even a syndrome from a clinical or mechanistic perspective, recognition of patients with features of both diseases is important to guide clinical care.

The clinical features, evaluation, and management of patients with asthma and COPD will be reviewed here. The diagnosis and management of asthma and COPD are discussed separately. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Chronic obstructive pulmonary disease: Diagnosis and staging" and "An overview of asthma management" and "Stable COPD: Overview of management".)

DEFINITION AND BACKGROUND — The term asthma-COPD overlap (ACO) has been used to identify patients with airway disease who have features of both asthma and COPD. However, the topic remains controversial and no single, universally accepted definition of ACO has emerged. Central to most of the proposed definitions are age >40 years, persistent airflow obstruction, and a history of asthma or evidence of partial bronchodilator reversibility (table 1) [3]. The term ACO has been preferred to asthma-COPD overlap syndrome (ACOS), as there is no single disease or “syndrome.”

In 2015, the Global Initiative for Asthma (GINA) and the Global Initiative for COPD (GOLD) released a joint statement describing what was then called ACOS, as "persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD" [4], identifiable in clinical practice by the features shared with both asthma and COPD.

In 2017, the American Thoracic Society and the National Heart, Lung, and Blood Institute published a joint workshop report on ACO. A major conclusion of the workshop is that ACO, like asthma and COPD, does not represent a single discrete disease entity [1]. It was suggested that ACO be used to describe patients, for instance, who have a long-standing history of asthma, in addition to having a modest smoking history and fixed airflow obstruction. At the same time, patients with COPD who have features of asthma, such as bronchodilator responsiveness and peripheral eosinophilia, could also be described as having ACO. While clinically, and likely pathologically, these patients remain distinct, both fall under the ACO umbrella.

Other groups have suggested additional major and minor criteria that may help to identify ACO patients and are further outlined in the table (table 1) [4-11]. In contrast, the 2020 GOLD Strategy update abandoned use of the term "asthma COPD overlap" arguing that asthma and COPD are different disorders that may share common features such as eosinophilia or some degree of reversibility [12]. GOLD emphasizes that asthma and COPD may coexist in an individual patient and that, if concurrent diagnoses are suspected, pharmacotherapy should primarily follow asthma guidelines although COPD specific therapy approaches may also be needed in some patients.

EPIDEMIOLOGY — It is difficult to establish an exact disease burden for ACO when no single definition has emerged. Estimates based on self-reported physician diagnosis or a combination of spirometry and symptom reporting suggest the prevalence of ACO in the general population is between 2 to 3 percent, with estimates for asthma and COPD in these same populations being roughly 5 to 17 percent for asthma and 2 to 12 percent for COPD [3]. However, when examining COPD patients specifically, the prevalence of ACO may be 25 percent [13], whereas when examining asthma patients, prevalence estimates for ACO range from 10 to 31 percent [3].

Despite significant heterogeneity within this patient population, studies suggest that ACO patients tend to be female and have a higher body mass index (BMI), lower socioeconomic status, and lower education level than patients with COPD [13-18]. Data regarding outcomes in patients with ACO compared with those with asthma or COPD without overlap are mixed, likely due to the significant heterogeneity of patients encompassed by this umbrella term. For example, in one population-based cohort followed for a median of nine years, patients with ACO and patients with COPD had similarly elevated risks of exacerbations and all-cause mortality compared with symptomatic smokers without COPD [19]. By contrast, other studies suggest ACO patients may have poorer disease control with respect to lung function, exacerbation rates, and respiratory symptoms than those with asthma or COPD without overlap [20,21]. The risk of lung cancer among patients with ACO appears similar to those with COPD and higher than other groups of smokers [22].

PATHOGENESIS — A common question when considering the pathogenesis of ACO is whether it is the result of a unique pathogenic process, or the result of additive pathologic processes of asthma and COPD coexisting in the same patient. Of course, even the pathogenesis of COPD itself is hotly debated. Similarly, the pathologic mechanisms underlying asthma are heterogeneous.

The Dutch hypothesis suggests both asthma and COPD stem from a single disease entity, but factors such as genetics and environmental exposures influence the clinical phenotype [23,24]. The British hypothesis contends separate origins for asthma and COPD, each with their own characteristic inflammatory drivers, including allergic inflammation in the former and factors such as chronic bacterial infection in the latter [25]. In the Dutch hypothesis worldview, ACO would lie in between asthma and COPD on the same continuous spectrum. Under the British hypothesis, unique factors would drive a specific type of inflammation that would make ACO distinct from asthma and COPD.

Conceptually, it is easy to conceive that tobacco smoking in an asthmatic patient might trigger increased neutrophilic inflammation, fixed airflow obstruction, and eventually COPD [26]. Conversely, it is also possible that an atopic patient without asthma begins primarily with COPD, but later develops an airway hyperresponsiveness and type 2-mediated airway inflammation. Allergen sensitization has been reported in older COPD patients [27]. Given that the clinical features of ACO patients significantly differ from patient to patient, it is likely that the predominant inflammatory mechanism differs from patient to patient.

CLINICAL FEATURES — Clinical features that have been described for ACO include age 40 years or older, respiratory symptoms including exertional dyspnea, persistent partially reversible airflow obstruction (without normalization of obstruction), and history of atopy and/or allergies [2,3]. Other clinical features may include ≥10 pack-years tobacco smoking and documented history of asthma before the age of 40 years (table 1). However, it is important to note that severe asthma often does not fully reverse to “normal.” (See 'Diagnosis' below.)

While cigarette and/or other air pollution exposures are not central to every definition, the absence of a history of exposure to noxious particles or gases (eg, tobacco smoking, indoor biomass fuel use) is uncommon.

As with both asthma and COPD, periodic exacerbations of these symptoms have been described in ACO. Patients with adult-onset asthma often have nonallergic asthma, so lack of an atopic history does not exclude asthma. On the other hand, the presence of nasal polyposis with or without other features of aspirin-exacerbated respiratory disease (AERD) may provide a sufficient explanation for recurrent exacerbations and persistent airflow limitation. (See "Aspirin-exacerbated respiratory disease".)

EVALUATION — The Global Initiative for Asthma (GINA) suggests that the evaluation of possible ACO closely matches the evaluation of asthma and COPD. A few steps that are more particular to patients with concomitant asthma and COPD are reviewed here. The evaluation and diagnosis of asthma and COPD are discussed separately. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Chronic obstructive pulmonary disease: Diagnosis and staging".)

History — In addition to determining the severity, frequency, and duration of respiratory symptoms (eg, dyspnea, cough, sputum) and exercise limitation, patients should be asked about any prior diagnosis or symptoms of asthma or allergic rhinitis.

A detailed history should be obtained regarding potential occupational, avocational, or domestic exposures to fumes or dusts, particularly tobacco smoke.

Laboratory — While these tests are not routinely obtained, when there is diagnostic uncertainty, an elevated total serum immunoglobulin E (IgE; >100 international units/mL), elevated peripheral blood eosinophil count (>300 cells/microL), and evidence of allergic disease (eg, skin testing or immunoassays for perennial allergen sensitivity) may point a clinician to asthma or ACO. Elevated sputum eosinophil counts, if available, are more common in asthma or ACO than COPD.

Testing for alpha-1 antitrypsin deficiency is advised for all patients with fixed airflow limitation. (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency", section on 'Evaluation and diagnosis'.)

Pulmonary function tests — Measurement of spirometry pre- and postbronchodilator is an essential component of the evaluation of airway disease. These tests are used to confirm airflow limitation (obstruction) and assess its reversibility (algorithm 1).

While airflow limitation is necessary for the diagnosis of ACO, it does not help differentiate among ACO, asthma, and COPD. (See "Office spirometry", section on 'Interpretation'.)

Typically, patients with ACO will demonstrate a bronchodilator response, which is defined by a postbronchodilator increase in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) of greater than 10 percent the predicted value; however, an increase in FEV1 or FVC by more than 15 percent of their predicted value is more common in asthma. Similarly, postbronchodilator FEV1 and FEV1/FVC generally remain abnormally low in patients with ACO. Postbronchodilator values in the normal range are more suggestive of asthma. (See "Pulmonary function testing in asthma", section on 'Bronchodilator responses'.)

Compared with patients who have COPD, patients with ACO tend to have greater increases in pulmonary function after extended treatment with inhaled glucocorticoids.

Reduced diffusing capacity of the lungs for carbon monoxide (DLCO) is more commonly a feature of COPD than asthma, but specific thresholds to help define ACO have not been determined (algorithm 1) [4].

Imaging — A chest radiograph is frequently obtained as part of the evaluation of persistent symptoms or an exacerbation. The chest radiograph may show hyperinflation in patients with ACO, but generally does not help with differentiating among asthma, COPD, and ACO. (See "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Additional testing'.).

High-resolution computed tomography may help if there is diagnostic uncertainty. Small airway disease in the absence of emphysema could still be consistent with ACO, although asthma (without COPD) and other diagnoses such as bronchiolitis obliterans should be considered (see 'Differential diagnosis' below). While some emphysema may be present in ACO, severe emphysema is more consistent with COPD [4].

DIAGNOSIS — The clinical label ACO has been used for patients with clinical features of both asthma and COPD (see 'Clinical features' above), although a specific distribution of features that secures a "diagnosis" of ACO has not been agreed upon [1]. It should be noted we do not specifically identify patients with “ACO” in our clinical practices but prefer to focus on disease specific phenotypes or the coexistence of both diseases (asthma and COPD).

Despite the lack of a well-accepted definition, the Global Initiative for Asthma (GINA) identifies a range of features that support a diagnosis of ACO, including [2,4]:

Age ≥40 years

Respiratory symptoms (eg, exertional dyspnea) are persistent, but variability in symptoms may be prominent

Airflow limitation not fully reversible, but with historical variability: Postbronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) <0.7 or lower limit of normal and bronchodilator increase in FEV1 >12 percent and 400 mL

History of doctor-diagnosed asthma at some point

History of atopy or allergies

Exposure to a risk factor (eg, ≥10 pack-years tobacco smoking or equivalent indoor/outdoor air pollution)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of ACO includes other airway diseases such as bronchiectasis, obliterative bronchiolitis, central airway obstruction, and diffuse panbronchiolitis [2]. The evaluation of other causes of dyspnea, such as heart failure, interstitial lung disease, and pulmonary vascular disease, is discussed separately. (See "Approach to the patient with dyspnea".)

Bronchiectasis is a condition of abnormal widening of the bronchi with obstruction to airflow (due to airway collapse). Bronchiectasis is suspected on the basis of prominent symptoms of a cough that is productive of mucopurulent sputum, recurrent chest infections, and sometimes hemoptysis. The diagnosis is usually established radiographically based on characteristic findings of bronchial wall thickening and luminal dilatation seen on CT scans. (See "Clinical manifestations and diagnosis of bronchiectasis in adults".)

Obliterative bronchiolitis, also known as bronchiolitis obliterans, is characterized by concentric fibrotic narrowing of the bronchiolar lumen. Obliterative bronchiolitis is most commonly seen following viral illness, inhalation injury, and transplantation (eg, bone marrow, lung) or in the context of rheumatic disease (table 2). Symptoms include progressive onset of cough and dyspnea associated with hypoxemia at rest or with exercise. Findings on computed tomography (CT) scans often include centrilobular bronchial wall thickening, bronchiolar dilation, tree-in-bud nodularity, and a mosaic pattern of attenuation of lung tissue density. (See "Overview of bronchiolar disorders in adults".)

Central airway obstruction can be caused by numerous benign and malignant processes and can mimic COPD with slowly progressive dyspnea on exertion followed by dyspnea with minimal activity. A flow-volume loop, which can be insensitive, and computed tomography with three-dimensional reconstruction can be helpful, but direct visualization is the gold standard for diagnosis. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Diffuse panbronchiolitis is characterized by bronchiolitis and chronic sinusitis and occurs mainly among individuals in East Asia. In the disease name, "diffuse" refers to the distribution of the lesions throughout both lungs and "pan" refers to the pathologic finding that the inflammation involves all layers of the respiratory bronchioles. A prominent clinical feature is cough productive of copious amounts of sputum. (See "Diffuse panbronchiolitis".)

INITIATION OF THERAPY

Nonpharmacologic therapy — General nonpharmacologic measures for patients with ACO are based on interventions that are useful in managing asthma and/or COPD. (See "An overview of asthma management" and "Stable COPD: Overview of management".)

Smoking cessation – Encouraging smoking cessation is an essential step in the management of ACO for all individuals who smoke. Similarly, avoidance of exposure to other sources of smoke and irritant inhalants at home or at work is prudent. (See "Overview of smoking cessation management in adults".)

Vaccination – Infection is a common cause of exacerbation in both asthma and COPD. An annual influenza vaccine should be given to all adults, particularly those with COPD or ACO. Vaccination against pneumococcus reduces exacerbations and community-acquired pneumonia in COPD and presumably also ACO. (See "Seasonal influenza vaccination in adults" and "Pneumococcal vaccination in adults".)

Inhaler technique – As the majority of medications for ACO are delivered by inhaler, education about proper inhaler technique should be provided and reviewed again at subsequent visits. (See "The use of inhaler devices in adults".)

Allergen avoidance – For patients with a suspected allergic contribution to ACO, allergen avoidance may reduce symptoms. (See "Allergen avoidance in the treatment of asthma and allergic rhinitis".)

Pulmonary rehabilitation – Pulmonary rehabilitation programs are clearly helpful for patients with COPD and can be excellent ancillary resources for education about inhaler technique and maintaining as active a lifestyle as possible. (See "Pulmonary rehabilitation".)

Pharmacotherapy — Initial strategies for pharmacotherapy outlined by the joint Global Initiative for Asthma/Global Initiative for COPD statement on ACO are based on expert opinion [2,12]. Formal data are limited, as clinical trials of medications for asthma and COPD have traditionally excluded patients with features of ACO. In general, we use an approach similar to that for asthma with inclusion of inhaled glucocorticoids (ICS; also called inhaled corticosteroids) in the regimen and a stepwise adjustment based on the response to medications.

All patients with ACO should have immediate access to an inhaled bronchodilator with a rapid onset of action (eg, short-acting beta agonist, short-acting muscarinic antagonist, or combination) for as-needed symptom relief.

In accordance with the Global Initiative for Asthma (GINA) strategy, we suggest regular therapy with a regimen that includes ICS in low to moderate doses. The addition of a long-acting beta-agonist (LABA) and/or long-acting muscarinic antagonist (LAMA) may be necessary to control symptoms. However, LABA monotherapy should be avoided, as in asthma.

ICS are considered appropriate in ACO, as they are a mainstay of asthma therapy [28]. Furthermore, accumulating evidence suggests that there is a relationship between greater blood eosinophil levels and ICS response in COPD [29,30]. In contrast, initial treatment of patients with COPD is based on bronchodilator therapy with LAMAs and LABAs, prescribed alone or in combination; ICS are not used as monotherapy for COPD. (See "Stable COPD: Initial pharmacologic management".)

The rationale for initial pharmacotherapy with ICS is based on the following observations:

Avoidance of LABA monotherapy in ACO – While LABA and/or LAMA therapy are given relatively equal weight and are a starting choice for maintenance therapy in COPD [12], LABA monotherapy is avoided in asthma due to results from Salmeterol Multicenter Asthma Research Trial (SMART) [31]. SMART was a 28-week, randomized trial comparing salmeterol administered via metered-dose inhaler versus a placebo. An interim analysis in 26,355 patients found an increase in respiratory-related deaths and asthma-related deaths, particularly among African American patients. As this study did not require ICS as maintenance therapy, concerns were raised about the safety of LABA therapy alone in asthma. Subsequent data have been reassuring regarding the safety of combination ICS-LABA inhalers in patients with asthma. Therefore, ICS-LABA combination inhalers can be used in ACO, but LABA monotherapy should be avoided.

LABA-ICS – A randomized, open-label, crossover study in 16 patients with ACO (defined as the combination of fixed airflow obstruction with airway hyperresponsiveness demonstrated by methacholine inhalation challenge) demonstrated a significant improvement in forced expiratory volume in one second (FEV1) after four weeks of once daily fluticasone furoate/vilanterol, compared with a run-in phase of twice daily fluticasone propionate-salmeterol [32].

Large trials that assess clinically important outcomes in patients with well-defined ACO are needed.

PERSISTENT SYMPTOMS OR EXACERBATIONS — A portion of patients with ACO may continue to have exercise limitation or frequent exacerbations despite therapy with inhaled glucocorticoids (ICS). Virtually no data exist to guide subsequent adjustments in therapy; a stepwise approach based on symptoms, exacerbations, and response to therapy is reasonable, similar to the approach used in asthma [2,12,28].

Triple therapy (LAMA-LABA-ICS) — For patients with persistent symptoms and/or exacerbations despite long-acting beta-agonist (LABA)/ICS or long-acting muscarinic antagonist (LAMA)/ICS, we suggest a trial of triple therapy (LAMA-LABA-ICS). A randomized, open-label crossover pilot study in 17 patients with ACO found that adding umeclidinium (LAMA) to fluticasone furoate/vilanterol (ICS/LABA) achieved a greater improvement in forced expiratory volume in one second (FEV1) after four weeks, than continuing fluticasone furoate/vilanterol without umeclidinium [33]. Support for triple therapy also comes from the experience in patients with severe persistent asthma or COPD with recurrent exacerbations. (See "Stable COPD: Follow-up pharmacologic management", section on 'General approach to patients with exacerbations'.)

Biologic agents — Patients with persistent symptoms or exacerbations despite triple therapy should be evaluated for features, such as sensitivity to perennial allergens, elevated total serum IgE, and/or peripheral blood eosinophilia, that might suggest a response to one or more of the biologic agents that have been developed for asthma (table 3). While awaiting data in patients with ACO, we typically use the same criteria that are used in severe persistent asthma. The use of these agents in severe asthma is described separately. (See "Treatment of severe asthma in adolescents and adults", section on 'Persistently uncontrolled asthma'.)

The following sections describe the limited data on the use of biologic agents in patients with COPD that may inform selection of therapy in those who have features of ACO.

Anti-IgE therapy — Anti-IgE therapies, such as omalizumab, reduce exacerbations and modestly improve symptoms in patients with allergic asthma with elevated serum immunoglobulin E (IgE) levels and sensitivity to perennial allergens [34,35] and may be of benefit in ACO [36-40]. (See "Anti-IgE therapy".)

A post-hoc analysis from a 48-week observational study of omalizumab examined patients with asthma who were not excluded for having comorbid COPD or a current or past history of smoking cigarettes [36]. Using a variety of ACO definitions, patients within the trial who met criteria for ACO demonstrated similar improvements in exacerbation rates and symptoms as non-ACO patients when compared with rates before the initiation of omalizumab.

Data from patients in the Australian Xolair Registry who also had a diagnosis of COPD based on either physician assessment or fixed airflow obstruction demonstrated improved asthma control and health-related quality of life (QOL) scores, though no significant change in FEV1 [37].

A small case series of 10 patients diagnosed with ACO based on low lung function, limited reversibility of airway obstruction, hyperinflation, dyspnea, and episodic wheezing demonstrated decreased interleukin (IL)-4 and improved pulmonary symptoms (dyspnea, wheezing, bronchial hyperresponsiveness) [38]. In small trials such as this, it is difficult to determine whether the patients studied indeed had ACO or had severe asthma that was not fully reversible postbronchodilator.

Anti-IL-5/IL-5 receptor alpha (IL-5Ra) therapies — IL-5 is a key mediator in eosinophil differentiation, maturation, and tissue migration. Several anti-IL-5 and anti-IL-5Ra monoclonal antibodies (eg, benralizumab, mepolizumab, reslizumab) are approved as add-on maintenance treatment in patients with severe asthma and eosinophilia. In asthma, these medications have been demonstrated to reduce exacerbations, improve symptoms and QOL, and decrease systemic glucocorticoid usage [41-43]. (See "Treatment of severe asthma in adolescents and adults", section on 'Anti-IL-5 therapy'.)

While an initial phase 2 study of benralizumab demonstrated a trend towards exacerbation reduction in COPD patients with blood eosinophil concentrations of 200 cells per microL or more [44], the results of two phase 3 studies in COPD were negative.

Data for mepolizumab in COPD have been equally contradictory. A phase 3 study in COPD patients with blood eosinophil counts at ≥150 cells/microL at screening or ≥300 cells/microL in the prior year showed a clinically and statistically significant reduction in moderate or severe exacerbations, while the parallel study was negative [45]. Therefore, further data will be needed to identify whether there is a subpopulation of ACO patients that might benefit.

IL-4 receptor alpha (IL-4Ra) and IL-13 therapies — IL-4 and IL-13 are cytokines that play a role in allergic inflammation through recruitment of mast cells and eosinophils to sites of allergic inflammation and also induction of goblet cell metaplasia [46]. The anti-IL-4Ra antibody dupilumab, which targets both the IL-13 and IL-4 pathways, improves lung function and reduces exacerbations in severe asthma, with greater benefit seen in patients with higher blood eosinophil levels [47,48]. A large, phase 3, randomized study found dupilumab to reduce exacerbation frequency and improve both lung function and quality of life for patients with frequent COPD exacerbations, chronic bronchitis, and blood eosinophil levels >300 cells/microL [49]. However, that study specifically excluded patients with a current diagnosis of asthma or history of asthma. The success of this trial suggests that dupilumab (and other biologics) may not only be useful for the treatment of ACO with eosinophilia, but also that clinical response to biologic therapies may refine our definition of ACO itself. (See "Treatment of severe asthma in adolescents and adults", section on 'Anti-lL-4 receptor alpha subunit antibody (dupilumab)' and "Management of refractory chronic obstructive pulmonary disease", section on 'Frequent exacerbations despite azithromycin or roflumilast'.)

Two anti-IL-13 antibodies, lebrikizumab and tralokinumab, both failed to reduce asthma exacerbations in phase 3 clinical trials and are not available for clinical use [50,51]. (See "Investigational agents for asthma", section on 'Anti-IL-13 antibodies'.)

FUTURE DIRECTIONS — Research efforts are needed to better understand asthma and COPD phenotypes and what types of biomarkers (physiologic, radiologic, or biologic) help to distinguish patients that are most responsive to specific therapies.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in adolescents and adults" and "Society guideline links: Chronic obstructive pulmonary disease".)

SUMMARY AND RECOMMENDATIONS

Asthma and chronic obstructive pulmonary disease (COPD) have characteristic clinical features, but patients with features of both asthma and COPD are commonly seen in clinical practice. The term asthma-COPD overlap (ACO) has been used to identify patients with airway disease who have features of both asthma and COPD, but there is no single, universally accepted definition of ACO (table 1). Further, ACO is likely not a single disease, nor even a syndrome from a clinical or mechanistic perspective. However, recognition of patients with both diseases are important in order to guide clinical care. (See 'Definition and background' above.)

The prevalence of ACO in the general population has been estimated to be between 2 and 3 percent, with estimates for asthma and COPD being roughly 5 to 17 percent and 2 to 12 percent, respectively. However, it is difficult to establish an exact disease burden for ACO in the absence of consensus regarding the exact definition. (See 'Epidemiology' above.)

As with asthma and COPD, significant heterogeneity of patients exists within the ACO umbrella and likely represents a range of underlying disease mechanisms as opposed to a single disease entity. (See 'Pathogenesis' above.)

The evaluation of suspected ACO closely matches the evaluation of asthma and COPD and focuses on demonstrating airflow limitation and assessing the degree of bronchodilator reversibility. Historical information about potential atopy is important to differentiating asthma, COPD, and ACO; a chest radiograph is helpful to exclude other causes of dyspnea. While not routinely obtained, a total serum immunoglobulin E (IgE), peripheral blood eosinophil count, and skin testing or immunoassays for perennial allergen sensitivity and/or high-resolution computed tomography can help if there is diagnostic uncertainty. (See 'Evaluation' above.)

A diagnosis of ACO is based on a combination of clinical features, although not all are required: age ≥40 years; airflow limitation that is not fully reversible; improvement in forced expiratory volume in one second (FEV1) by 10 percent of predicted value after bronchodilator administration; a history of asthma diagnosed by a doctor; a history of atopy or allergies; and exposure to noxious agents such as cigarette smoke (eg, ≥10 pack years). A peripheral blood eosinophil count ≥300 cells/microL is supportive of a diagnosis of ACO or asthma. (See 'Diagnosis' above.)

General nonpharmacologic measures for patients with ACO are based on interventions that are useful in managing asthma and/or COPD and include smoking cessation, annual vaccination against influenza and age-appropriate vaccination against pneumococcus, education about the correct technique for all inhalers prescribed, allergen avoidance for those with known allergic sensitization, and pulmonary rehabilitation. (See 'Nonpharmacologic therapy' above.)

All patients with ACO should have immediate access to an inhaled bronchodilator with a rapid onset of action (eg, short-acting beta agonist, short-acting muscarinic antagonist, or combination) for as needed symptom relief. (See 'Pharmacotherapy' above.)

For patients with ACO and mild to moderate symptoms, we suggest using a regimen that includes inhaled glucocorticoids (ICS) in low to moderate doses (Grade 2B), with or without a long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) to control symptoms and prevent exacerbations. LABA monotherapy should be avoided. (See 'Pharmacotherapy' above.)

As with asthma, therapy is escalated if needed to maintain control of symptoms and reduce exacerbations. This may include an increase in the dose of ICS and/or addition of a LAMA, ICS, and LABA. (See 'Triple therapy (LAMA-LABA-ICS)' above.)

Patients with persistent symptoms or exacerbations despite triple inhaled therapy should be evaluated for features that might suggest benefit from one of the biologic agents (eg, omalizumab, mepolizumab, benralizumab, reslizumab) that have been developed for asthma (eg, sensitivity to perennial allergens, elevated total serum IgE, and/or peripheral blood eosinophilia). While awaiting data in patients with ACO, we typically use the same criteria that are used in severe persistent asthma when selecting among biologic agents (table 3). (See 'Biologic agents' above.)

  1. Woodruff PG, van den Berge M, Boucher RC, et al. American Thoracic Society/National Heart, Lung, and Blood Institute Asthma-Chronic Obstructive Pulmonary Disease Overlap Workshop Report. Am J Respir Crit Care Med 2017; 196:375.
  2. Global Initiative for Asthma (GINA). Diagnosis and initial treatment of asthma, COPD, and asthma-COPD overlap: A joint project of GINA and GOLD updated April 2017. https://ginasthma.org/wp-content/uploads/2019/11/GINA-GOLD-2017-overlap-pocket-guide-wms-2017-ACO.pdf (Accessed on November 18, 2019).
  3. Leung JM, Sin DD. Asthma-COPD overlap syndrome: pathogenesis, clinical features, and therapeutic targets. BMJ 2017; 358:j3772.
  4. goldcopd.org/wp-content/uploads/2016/04/GOLD_ACOS_2015.pdf (Accessed on October 16, 2019).
  5. Cosio BG, Soriano JB, López-Campos JL, et al. Defining the Asthma-COPD Overlap Syndrome in a COPD Cohort. Chest 2016; 149:45.
  6. Gibson PG, Simpson JL. The overlap syndrome of asthma and COPD: what are its features and how important is it? Thorax 2009; 64:728.
  7. Sin DD, Miravitlles M, Mannino DM, et al. What is asthma-COPD overlap syndrome? Towards a consensus definition from a round table discussion. Eur Respir J 2016; 48:664.
  8. Cataldo D, Corhay JL, Derom E, et al. A Belgian survey on the diagnosis of asthma-COPD overlap syndrome. Int J Chron Obstruct Pulmon Dis 2017; 12:601.
  9. Soler-Cataluña JJ, Cosío B, Izquierdo JL, et al. Consensus document on the overlap phenotype COPD-asthma in COPD. Arch Bronconeumol 2012; 48:331.
  10. Koblizek V, Chlumsky J, Zindr V, et al. Chronic Obstructive Pulmonary Disease: official diagnosis and treatment guidelines of the Czech Pneumological and Phthisiological Society; a novel phenotypic approach to COPD with patient-oriented care. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013; 157:189.
  11. Miravitlles M, Alvarez-Gutierrez FJ, Calle M, et al. Algorithm for identification of asthma-COPD overlap: consensus between the Spanish COPD and asthma guidelines. Eur Respir J 2017; 49.
  12. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. https://www.goldcopd.org (Accessed on December 02, 2019).
  13. Alshabanat A, Zafari Z, Albanyan O, et al. Asthma and COPD Overlap Syndrome (ACOS): A Systematic Review and Meta Analysis. PLoS One 2015; 10:e0136065.
  14. van Boven JF, Román-Rodríguez M, Palmer JF, et al. Comorbidome, Pattern, and Impact of Asthma-COPD Overlap Syndrome in Real Life. Chest 2016; 149:1011.
  15. Cosentino J, Zhao H, Hardin M, et al. Analysis of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome Defined on the Basis of Bronchodilator Response and Degree of Emphysema. Ann Am Thorac Soc 2016; 13:1483.
  16. Kumbhare S, Pleasants R, Ohar JA, Strange C. Characteristics and Prevalence of Asthma/Chronic Obstructive Pulmonary Disease Overlap in the United States. Ann Am Thorac Soc 2016; 13:803.
  17. Chung JW, Kong KA, Lee JH, et al. Characteristics and self-rated health of overlap syndrome. Int J Chron Obstruct Pulmon Dis 2014; 9:795.
  18. Dodd KE, Wood J, Mazurek JM. Mortality Among Persons with Both Asthma and Chronic Obstructive Pulmonary Disease Aged ≥25 Years, by Industry and Occupation - United States, 1999-2016. MMWR Morb Mortal Wkly Rep 2020; 69:670.
  19. Çolak Y, Nordestgaard BG, Lange P, et al. Prognosis of Patients with Chronic Obstructive Pulmonary Disease Not Eligible for Major Clinical Trials. Am J Respir Crit Care Med 2022; 206:271.
  20. Hardin M, Silverman EK, Barr RG, et al. The clinical features of the overlap between COPD and asthma. Respir Res 2011; 12:127.
  21. Vaz Fragoso CA, Murphy TE, Agogo GO, et al. Asthma-COPD overlap syndrome in the US: a prospective population-based analysis of patient-reported outcomes and health care utilization. Int J Chron Obstruct Pulmon Dis 2017; 12:517.
  22. Charokopos A, Braman SS, Brown SAW, et al. Lung Cancer Risk among Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap. Ann Am Thorac Soc 2021; 18:1894.
  23. ORIE NG. Correlations of emphysema and asthmatic constitution. Acta Allergol 1961; 16:407.
  24. Orie NGM, Sluiter JH, de Vries K. The host factor in bronchitis. In: Bronchitis: An International Symposium, Royal Vangorcum, Assen 1960. p.43.
  25. Barnes PJ. Against the Dutch hypothesis: asthma and chronic obstructive pulmonary disease are distinct diseases. Am J Respir Crit Care Med 2006; 174:240.
  26. Siew LQC, Wu SY, Ying S, Corrigan CJ. Cigarette smoking increases bronchial mucosal IL-17A expression in asthmatics, which acts in concert with environmental aeroallergens to engender neutrophilic inflammation. Clin Exp Allergy 2017; 47:740.
  27. Itabashi S, Fukushima T, Aikawa T, et al. Allergic sensitization in elderly patients with chronic obstructive pulmonary disease. Respiration 1990; 57:384.
  28. 2023 Global Initiative for Asthma (GINA) Report: Global Strategy for Asthma Management and Prevention. www.ginasthma.org/2023-gina-main-report (Accessed on May 15, 2023).
  29. Pascoe S, Barnes N, Brusselle G, et al. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med 2019; 7:745.
  30. Bafadhel M, Peterson S, De Blas MA, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med 2018; 6:117.
  31. Nelson HS, Weiss ST, Bleecker ER, et al. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006; 129:15.
  32. Ishiura Y, Fujimura M, Shiba Y, et al. A comparison of the efficacy of once-daily fluticasone furoate/vilanterole with twice-daily fluticasone propionate/salmeterol in asthma-COPD overlap syndrome. Pulm Pharmacol Ther 2015; 35:28.
  33. Ishiura Y, Fujimura M, Ohkura N, et al. Effect of triple therapy in patients with asthma-COPD overlap
. Int J Clin Pharmacol Ther 2019; 57:384.
  34. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001; 108:184.
  35. Lemanske RF Jr, Nayak A, McAlary M, et al. Omalizumab improves asthma-related quality of life in children with allergic asthma. Pediatrics 2002; 110:e55.
  36. Hanania NA, Chipps BE, Griffin NM, et al. Omalizumab effectiveness in asthma-COPD overlap: Post hoc analysis of PROSPERO. J Allergy Clin Immunol 2019; 143:1629.
  37. Maltby S, Gibson PG, Powell H, McDonald VM. Omalizumab Treatment Response in a Population With Severe Allergic Asthma and Overlapping COPD. Chest 2017; 151:78.
  38. Yalcin AD, Celik B, Yalcin AN. Omalizumab (anti-IgE) therapy in the asthma-COPD overlap syndrome (ACOS) and its effects on circulating cytokine levels. Immunopharmacol Immunotoxicol 2016; 38:253.
  39. Tat TS, Cilli A. Omalizumab treatment in asthma-COPD overlap syndrome. J Asthma 2016; 53:1048.
  40. Kupryś-Lipińska I, Pałczyński C, Molinska J, Kuna P. Omalizumab therapy in a patient with severe asthma and co-existing chronic obstructive pulmonary disease. Postepy Dermatol Alergol 2019; 36:239.
  41. Castro M, Wenzel SE, Bleecker ER, et al. Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med 2014; 2:879.
  42. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014; 371:1189.
  43. Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015; 3:355.
  44. Brightling CE, Bleecker ER, Panettieri RA Jr, et al. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med 2014; 2:891.
  45. Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med 2017; 377:1613.
  46. Kau AL, Korenblat PE. Anti-interleukin 4 and 13 for asthma treatment in the era of endotypes. Curr Opin Allergy Clin Immunol 2014; 14:570.
  47. Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med 2018; 378:2486.
  48. Rabe KF, Nair P, Brusselle G, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med 2018; 378:2475.
  49. Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med 2023; 389:205.
  50. Hanania NA, Korenblat P, Chapman KR, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med 2016; 4:781.
  51. Panettieri RA Jr, Sjöbring U, Péterffy A, et al. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med 2018; 6:511.
Topic 122856 Version 14.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟