Concomitant asthma and COPD

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 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]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) and several other guideline groups have moved away from this term, preferring to categorize these patients as having two coexisting diseases [3]. While we agree that 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. Certain clinical decisions require additional consideration for these patients compared with those who have either asthma or COPD alone.

The clinical features, evaluation, and management of patients with concomitant asthma and COPD will be reviewed here. The diagnosis and management of asthma and COPD individually are discussed separately.

●(See "Asthma in adolescents and adults: Evaluation and diagnosis".)

●(See "Chronic obstructive pulmonary disease: Diagnosis and staging".)

●(See "An overview of asthma management in children and adults".)

●(See "Stable COPD: Overview of management".)

TERMINOLOGY AND BACKGROUND — 

The term asthma-COPD overlap (ACO) has historically been used to identify patients with airway disease who have features of both asthma and COPD. However, this nomenclature remains controversial, and no universally accepted definition of ACO has emerged. Despite some involvement in popularizing "asthma-COPD overlap syndrome" in 2015 [4], the Global Initiative for Asthma (GINA) and the Global Initiative for Obstructive Lung Disease (GOLD) now discuss "coexisting" or "concomitant" asthma and COPD in their reports [3,5]. This approach emphasizes that each disease is separate even though they may share common features such as eosinophilia or some degree of bronchodilator reversibility. Patients with features of both diseases are themselves a heterogeneous group that likely represents a variety of underlying mechanisms of airway pathology.

In 2017, the American Thoracic Society and the National Heart, Lung, and Blood Institute published a joint workshop report on ACO [1]. A major conclusion of the workshop was that ACO, like asthma and COPD, does not represent a single discrete disease entity. For example, ACO may describe patients 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, are also reasonably described as having ACO. While clinically (and likely pathologically) these patient groups are distinct, both fall under the ACO umbrella.

The 2020 GOLD Strategy update abandoned use of the term "asthma-COPD overlap" [6]; GINA has also opted to eschew this nomenclature, although notes that ACO is a reasonable "simple descriptor" for patients with features of both diseases [5]. Both guidelines agree that the identification of patients with concomitant asthma and COPD clinical features is important for the safety and clinical efficacy of subsequent management.

EPIDEMIOLOGY AND NATURAL HISTORY — 

It is difficult to establish an exact disease burden for coexistent asthma and COPD. Estimates based on self-reported clinician diagnosis or a combination of spirometry and symptom reporting suggest the prevalence 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 [7]. However, when examining COPD patients specifically, the prevalence of asthma features may be 25 percent [8], whereas when examining asthma patients, prevalence estimates for COPD features range from 10 to 31 percent [7].

Despite significant heterogeneity within this patient population, studies suggest that patients with both asthma and COPD tend to be female and have a higher body mass index (BMI), lower socioeconomic status, and lower education level than patients with COPD alone [8-13].

Unsurprisingly, data regarding outcomes in patients with concomitant asthma and COPD 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, both patients with COPD and comorbid asthma and patients with COPD alone had similarly elevated risks of exacerbations and all-cause mortality compared with symptomatic smokers without COPD [14]. 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 [15,16]. The risk of lung cancer among patients with ACO appears similar to those with COPD and higher than other groups of smokers [17].

PATHOGENESIS — 

It is not clear whether there is an unusual pathogenic process for patients with concomitant asthma and COPD or whether the clinical picture is fully the result of the additive pathophysiology of each disease in the same patient. Of course, the underlying etiologies of both asthma and COPD are heterogeneous and not fully understood, making this question very difficult to study.

Speculatively, the "Dutch hypothesis" suggests that both asthma and COPD stem from a single disease entity, but factors such as genetics and environmental exposures influence the clinical phenotype [18,19]. In contrast, the "British hypothesis" contends separate origins for asthma and COPD, each with its own characteristic inflammatory drivers, including allergic inflammation in the former and factors such as chronic bacterial infection in the latter [20]. In the Dutch hypothesis worldview, patients with features of both diseases would lie in the spectrum between asthma and COPD. Under the British hypothesis, unique factors would drive a specific type of inflammation that would make patients with both diseases distinct from either disease alone.

Conceptually, it is easy to conceive that tobacco smoking in an asthmatic patient might trigger increased neutrophilic inflammation, fixed airflow obstruction, and eventually COPD [21]. 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 [22]. Given that the clinical features of patients with both asthma and COPD significantly differ from patient to patient, it is likely that the predominant inflammatory mechanism differs from patient to patient as well.

Further adding to this discussion is the recognition that some patients with COPD have elements of Type 2 inflammation, as indicated by elevated sputum or blood eosinophils, without other asthmatic features. These patients demonstrate the greatest benefit from inhaled corticosteroids and [23,24] may also benefit from biologics targeted at Type 2 inflammation [25,26].

CLINICAL FEATURES — 

Asthma and COPD share features of chronic obstructive lung diseases, including variable symptoms of exertional dyspnea, wheezing, chest tightness, and cough, as well as intermittent exacerbations of these symptoms that require more intensive bronchodilator and/or glucocorticoid therapies. Patients younger than 40 years old are highly unlikely to have COPD. Many of the clinical features of asthma versus COPD have been incorporated into various proposed diagnostic criteria for asthma-COPD overlap (ACO) (table 1) [7,27-32].

●Clinical features suspicious for concomitant COPD in older adults with asthma – In older adults with asthma, concomitant COPD typically arises from ongoing exposures to noxious particles or gases (eg, tobacco smoking, second-hand smoking, indoor biomass fuel use). New development of chronic cough and sputum production is suspicious, especially if there is significant daily sputum in the absence of triggers or other worsening symptoms. Finally, a worsening of symptoms over time and failure to feel improvement to baseline after bronchodilator therapy may be seen. Distinguishing these features from chronic airway remodeling due to persistent severe asthma can be challenging. (See 'Diagnosis' below.)

●Clinical features suspicious for concomitant asthma in patients with COPD – Allergic symptoms, such as current or historical atopy, seasonal allergies, food allergies, and allergic rhinitis, may raise suspicion for asthma. The presence of nasal polyposis with or without other features of aspirin-exacerbated respiratory disease (AERD) is highly suggestive. However, patients with adult-onset asthma often have nonallergic asthma, so lack of an atopic history does not exclude the diagnosis. (See "Aspirin-exacerbated respiratory disease".)

Wheezing, chest tightness, or dyspnea that is triggered by exercise, emotions, dusts, or exposure to allergens are each more consistent with asthma. In addition, patients with concomitant asthma may experience a very robust symptom improvement with initial treatment, which is less common for patients with COPD alone.

EVALUATION — 

Patients with suspicion for asthma and COPD should receive the appropriate diagnostic evaluation for both conditions. Features that may suggest concomitant presence of both conditions are discussed here. The evaluation and diagnosis of asthma and COPD individually 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, atopy, or allergic rhinitis.

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

Laboratory — Elevated total serum immunoglobulin E (IgE; >100 international units/mL), peripheral blood eosinophil count (>300 cells/microL), and fraction of exhaled nitric oxide (>50 ppb) are markers of Type 2 inflammation. Type 2 inflammation can be seen both in patients with asthma as well as in a subset of patients with COPD alone without other asthmatic features. Therefore, laboratory evidence alone will not necessarily distinguish a patient with asthma from one with COPD and Type 2 inflammation. Nevertheless, elevated Type 2 markers increase the likelihood of response to inhaled glucocorticoids and/or biologics that target Type 2 inflammation. (See 'Pharmacotherapy' below.)

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

Pulmonary function tests — Measurement of pre- and postbronchodilator spirometry 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). The "typical" pattern that is suspicious for concomitant asthma and COPD is a combination of robust bronchodilator response without complete reversibility ("partial-reversibility"). However, the diagnosis of concomitant asthma and COPD cannot be made solely on the basis of spirometry for the following reasons:

●While airflow limitation is necessary for the diagnosis of COPD, it does not help differentiate asthma from COPD (however, normal postbronchodilator pulmonary function is not consistent with the diagnosis of COPD). (See "Office spirometry", section on 'Interpretation'.)

●Patients with either asthma or COPD may 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 of the predicted value [33,34]. While an increase in FEV₁ or FVC by more than 15 percent of their predicted value may be more common in asthma, it may also still be seen in COPD. (See "Office spirometry", section on 'Post-bronchodilator spirometry' and "Pulmonary function testing in asthma", section on 'Bronchodilator responses'.)

●Likewise, although persistent postbronchodilator ("fixed") obstruction is a hallmark feature of COPD, patients with asthma may also demonstrate fixed obstruction without having concomitant COPD. For example, patients with asthma who are tested while having significant symptoms may have residual obstruction, and those with longstanding severe disease may develop airway remodeling. (See "Pulmonary function testing in asthma", section on 'Bronchodilator responses'.)

Additional pulmonary function testing, such as lung volumes and diffusing capacity, can be helpful when assessing for possible COPD in a patient with asthma:

●Hyperinflation and severe air-trapping are much more common with emphysema than in those with asthma (in the absence of a current exacerbation).

●Reduced diffusing capacity of the lungs for carbon monoxide (DLCO) is also more commonly a feature of COPD than asthma, although specific thresholds to help define ACO have not been determined (algorithm 1) [4]. (See "Diffusing capacity for carbon monoxide", section on 'Interpretation'.)

Longitudinal assessment can also be helpful, as patients with concomitant asthma and COPD tend to have greater increases in pulmonary function after extended treatment with inhaled glucocorticoids than those with COPD alone.

Imaging — High-resolution computed tomography may be useful if there is diagnostic uncertainty. Specifically, the presence of emphysema is unique to COPD [4]. Airway wall-thickening is common in both conditions individually and therefore does not assist in diagnosis. Small airway disease (such as air-trapping and mosaicism) in the absence of emphysema may be consistent with both asthma and COPD, asthma (without COPD), and alternative diagnoses such as bronchiolitis obliterans. (See 'Differential diagnosis' below.)

DIAGNOSIS — 

Because asthma and COPD have overlapping clinical features and diagnostic criteria that are not mutually exclusive, it is very difficult to distinguish concomitant disease from a single disease with some atypical features (eg, asthma with fixed airway remodeling or COPD with Type 2 inflammation). Various systems have been proposed (table 1), but no specific distribution of features that secures a "diagnosis" of "asthma-COPD overlap" (ACO) or "concomitant asthma and COPD" has been agreed upon [1]. Given these difficulties, we do not specifically identify patients with "ACO" in our clinical practices but prefer to focus on disease-specific phenotypes and treat them accordingly.

Despite the lack of a well-accepted consensus definition, patients with concomitant asthma and COPD should have persistent postbronchodilator airflow obstruction along with some clinical features of both asthma and COPD. These supportive features may include [2,4]:

●Age ≥40 years

●Respiratory symptoms (eg, exertional dyspnea) that are persistent, but with high variability

●Airflow limitation not fully reversible, but with historical variability or robust bronchodilator response (eg, >15 percent of predicted forced expiratory volume in one second [FEV₁])

●Elevated type 2 inflammatory markers (IgE, peripheral eosinophils, or fraction of exhaled nitric oxide [FeNO])

●History of clinician-diagnosed asthma

●History of atopy or allergies

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

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of obstructive lung disease includes other airway diseases such as bronchiectasis, sarcoidosis, 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 usually suspected on the basis of prominent 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 on computed tomography (CT) scan. Bronchiectasis may arise from many causes, and treatment can depend on the underlying etiology. For example, adult-onset cystic fibrosis (CF) may be amenable to CF transmembrane conductance regulator modulator therapy. (See "Clinical manifestations and diagnosis of bronchiectasis in adults", section on 'Etiologies'.)

●Sarcoidosis is a systemic granulomatous disease that most frequently affects the lungs. Although often considered an interstitial lung disease that leads to restriction, sarcoidosis can also have airway involvement, which may produce a fixed obstructive pattern on spirometry [35]. Sarcoidosis involving the airways can also respond to high-dose inhaled glucocorticoids. Sarcoidosis frequently, although not always, is also accompanied by bilateral hilar lymphadenopathy, pulmonary parenchymal infiltrates, or additional extrapulmonary features. (See "Clinical manifestations and diagnosis of sarcoidosis".)

●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 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 CT 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 both asthma and COPD are based on interventions that are useful in managing the diseases separately. (See "An overview of asthma management in children and adults" and "Stable COPD: Overview of management".)

●Smoking cessation – Encouraging smoking cessation is an essential step in the management of asthma and COPD 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 – Respiratory infection is a common cause of exacerbation in both asthma and COPD. Providers should strongly encourage age-appropriate vaccinations against influenza, pneumococcus, pertussis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus in all patients with asthma and/or COPD. Shingles (herpes zoster) vaccination is also appropriate. (See "Standard immunizations for nonpregnant adults".)

●Inhaler technique – As the majority of medications for asthma and COPD 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 and trigger avoidance – For patients with a suspected allergic contribution to their symptoms, allergen identification and avoidance may help reduce symptoms and exacerbations. Directed questions can help identify triggers both at home and in the workplace, and allergen testing may be appropriate. (See "Allergen avoidance in the treatment of asthma and allergic rhinitis" and "Trigger control to enhance asthma management" and "Occupational asthma: Management, prognosis, and prevention".)

●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 an active lifestyle. (See "Pulmonary rehabilitation".)

Pharmacotherapy — Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends that for patients with elements of both asthma and COPD, initial therapy should primarily follow asthma guidelines (table 3 and table 4) [3]. Among patients with asthma, long-acting bronchodilators are not used without anti-inflammatory therapy (ie, inhaled glucocorticoids) due to a risk of increased exacerbations and death [5,36]. In addition, all patients with asthma and impaired lung function should receive maintenance inhaled glucocorticoids to help reduce exacerbations and improve symptoms. Patients with concomitant asthma and COPD who have frequent exacerbations despite maximal inhaled therapies may benefit from asthma biologics or therapies for refractory COPD. (See "Management of refractory chronic obstructive pulmonary disease".)

Inhaled therapies — Low-dose ICS-LABA (step 3) (table 5) is the recommended initial therapeutic approach for patients with asthma who have low lung function (table 3). [5]. For patients with persistent exacerbations and/or symptoms despite medium-dose inhaled corticosteroids (ICS)-long-acting beta-agonists (LABA; step 4), we suggest triple therapy (ICS-LAMA [long-acting muscarinic antagonists]-LABA) rather than other options. Triple therapy is preferable due to strong evidence in favor of improved exacerbations and symptoms in patients with COPD. (See "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LAMA-LABA therapy' and "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LABA-ICS'.)

For patients with concomitant asthma and COPD who continue to have exacerbations despite triple therapy, we may begin therapeutic trials of agents that are helpful in refractory COPD. This can include a trial of add-on ensifentrine, where available, even though the trials supporting ensifentrine did not include patients with asthma or those on triple therapy (and included some patients not on any bronchodilator therapy). The standard dose of ensifentrine is 3 mg twice daily via nebulizer. Availability, cost, and insurance coverage may be practical barriers to ensifentrine use. (See "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LAMA-LABA-ICS'.)

Additional options for patients with a large component of COPD and persistent exacerbations include oral therapies for refractory COPD (algorithm 2). In patients with more allergy/asthma symptoms and elevated markers of Type 2 inflammation, biologic therapy may be more effective [2,5,6,37]. (See 'Biologic agents' below.)

Azithromycin — Low-certainty evidence suggests that chronic azithromycin therapy can modestly reduce exacerbations in patients with either asthma alone or COPD alone who continue to have frequent exacerbations despite inhaled therapies. The data in favor of this approach is stronger in COPD than in asthma, but the underlying mechanism is likely similar. As such, a trial of azithromycin is a reasonable alternative to biologic therapies in patients with concomitant asthma and COPD. The usual dose is 500 mg orally three times a week or 250 mg orally once daily. Azithromycin may contribute to a prolonged QT interval or hearing loss and may be less effective in active smokers. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Azithromycin and other long-term antibiotic therapy' and "Treatment of severe asthma in adolescents and adults", section on 'Macrolide antibiotics'.)

Biologic agents — Patients with persistent symptoms or exacerbations despite triple therapy should be evaluated for markers of Type 2 inflammation, such as sensitivity to perennial allergens, fraction of exhaled nitric oxide (FeNO), 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 6). The use of these agents in severe asthma is described separately. (See "Treatment of severe asthma in adolescents and adults", section on 'Persistently uncontrolled severe asthma'.)

Anti-IL-4 receptor alpha (IL-4R) therapy — Dupilumab has received regulatory approval in the United States [38] and Europe [39] for the treatment of patients with uncontrolled COPD despite inhaled therapies and elevated peripheral eosinophils. Dupilumab targets interleukin- (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 [40]. 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 [41,42]. Two large, phase 3, randomized studies 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 [25,26]. While these studies specifically excluded patients with a current diagnosis of asthma or history of asthma, dupilumab has already been shown to improve symptoms and lung function and decrease exacerbation frequency in asthma. The success of these two COPD trials suggests that dupilumab is effective among COPD patients with evidence of Type 2 inflammation. Patients with higher levels of FeNO may also be more likely to respond to dupilumab, although this biomarker is likely less useful in patients who are actively smoking. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Frequent exacerbations despite these agents' and "Treatment of severe asthma in adolescents and adults", section on 'Anti-IL-4 receptor alpha subunit antibody (dupilumab)'.)

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 quality of life, and decrease systemic glucocorticoid usage [43-45]. For patients with COPD, results of clinical trials have been inconsistent [46-49]. Results for the Matinee study were just reported, suggesting reduction in exacerbations among COPD patients on inhaled triple therapy. (See "Treatment of severe asthma in adolescents and adults", section on 'Anti-IL-5/5R antibodies' and "Stable COPD: Follow-up pharmacologic management", section on 'Future directions'.)

Anti-thymic stromal lymphopoietin (tezepelumab) — Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine. Tezepelumab is a human monoclonal immunoglobulin G-2-lambda antibody that binds TSLP and prevents its interaction with the TSLP receptor complex. Tezepelumab is already approved by the United States Food and Drug Administration (FDA) for add-on maintenance therapy in patients with severe asthma demonstrating reductions in asthma exacerbations. Data from a phase 2 study in COPD demonstrated a reduction in exacerbation frequency among patients with blood eosinophil counts ≥150 cells/microL [50]. There are currently no data in patients who have both asthma and COPD.

Anti-IgE therapy — Anti-IgE therapies, such as omalizumab, reduce exacerbations and modestly improve symptoms in patients with allergic asthma with elevated serum IgE levels and sensitivity to perennial allergens [51,52]. Limited observational data suggest anti-IgE therapies may be of benefit in concomitant asthma and COPD [53-57]. (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 [53]. Using a variety of concomitant asthma and COPD definitions, patients within the trial who met criteria for concomitant asthma and COPD demonstrated similar improvements in exacerbation rates and symptoms as other 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 clinician assessment or fixed airflow obstruction demonstrated improved asthma control and health-related quality of life scores, though no significant change in forced expiratory volume in one second (FEV₁) [54].

FUTURE DIRECTIONS — 

Research efforts are needed to better understand asthma and COPD phenotypes and what types of biomarkers (physiologic, radiologic, or biologic) help distinguish patients who 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

●Terminology and background – Asthma and 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 historically been used to identify patients with airway disease who have features of both asthma and COPD, but there is no single, universally accepted definition as there is no evidence suggesting it is a unique syndrome (table 1). The term ACO is less commonly used for this reason. However, recognition of patients with both diseases is important in order to guide appropriate clinical care. (See 'Terminology and background' above.)

●Pathogenesis – Significant heterogeneity exists among these patients, suggesting a range of underlying disease mechanisms rather than a single disease entity. (See 'Pathogenesis' above.)

●Clinical features – Asthma and COPD share features of chronic obstructive lung diseases, including variable symptoms of exertional dyspnea, wheezing, chest tightness, cough, as well as intermittent exacerbations of these symptoms that require more intensive bronchodilator and/or glucocorticoid therapies.

●Evaluation – The evaluation of patients with suspected concomitant asthma and COPD 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 and laboratory evaluation of Type 2 inflammation may be helpful in suggesting an asthma diagnosis. High-resolution CT may identify features specific to COPD. (See 'Evaluation' above.)

●Diagnosis – A diagnosis of concomitant asthma and COPD is based on a combination of clinical features consistent with both diseases, such as: age ≥40 years; airflow limitation that is not fully reversible; improvement in forced expiratory volume in one second (FEV₁) by 15 percent of predicted value after bronchodilator administration; a history of clinician-diagnosed asthma; a history of atopy or allergies; and exposure to noxious agents such as cigarette smoke (eg, ≥10 pack years). (See 'Diagnosis' above.)

●General measures – General nonpharmacologic measures for patients with asthma and COPD are similar to those used for each disease separately. They include smoking cessation, annual vaccination against respiratory illnesses, education about inhaler technique, allergen and trigger avoidance, and pulmonary rehabilitation. (See 'Nonpharmacologic therapy' above.)

●Pharmacotherapy – Initial inhaled therapy for patients with COPD and asthma should follow asthma treatment protocols given the increased safety and efficacy of including inhaled glucocorticoid therapy in patients with asthma (table 3). Given the reduced lung function present in those with asthma and COPD, the typical initial regimen in the absence of severe symptoms is low-dose inhaled corticosteroids (ICS)-long-acting beta-agonists (LABA; step 3).

For patients with asthma and COPD who continue to have exacerbations and symptoms despite moderate dose ICS-LABA (or other step 4 therapy), we suggest the use of triple therapy with ICS-long-acting muscarinic antagonists (LAMA)-LABA rather than other options (table 4) (Grade 2C). This regimen is highly effective for exacerbation prevention in COPD. (See "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LAMA-LABA therapy' and "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LABA-ICS'.)

Ensifentrine may be helpful for patients with asthma and COPD with persistent dyspnea or exacerbations despite triple therapy, although the data are very limited. Chronic azithromycin may also be helpful for these patients. (See "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LAMA-LABA-ICS' and "Management of refractory chronic obstructive pulmonary disease", section on 'Azithromycin and other long-term antibiotic therapy' and "Treatment of severe asthma in adolescents and adults", section on 'Macrolide antibiotics'.)

●Patients with persistent symptoms or exacerbations despite inhaled therapies should be evaluated for features that might suggest benefit from one of the biologic agents (eg, dupilumab, mepolizumab, tezepelumab) (table 6). (See 'Biologic agents' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Sally Wenzel, MD, who contributed to earlier versions of this topic review.