Bronchial asthma (asthma for short) and chronic obstructive pulmonary disease (COPD for short) are two different diseases, but in clinical practice it is sometimes not easy to clearly distinguish asthma from COPD. More complicated is the coexistence of asthma and COPD, known as asthma-COPD overlap syndrome (ACOS).
In early 2014, the Global Initiative for the Prevention and Treatment of Chronic Obstructive Lung (GOLD) update was released, with an additional chapter on ACOS (Introduction), suggesting that the GOLD and GINA scientific committees had jointly developed guidelines on ACOS, which would first be published in full in the GINA update. The GINA update was released in May 2014 with a new chapter 5, entitled “Diagnosis of asthma, chronic obstructive pulmonary disease and asthma-acute obstructive pulmonary overlap syndrome (ACOS): a joint project of GINA and GOLD” (hereafter referred to as the joint guideline).
The document was developed mostly on the basis of expert consensus, rather than so-called evidence-based medical evidence. Its objectives are threefold: (1) to identify patients with chronic airflow limitation disease; (2) to distinguish asthma from chronic obstructive pulmonary disease and ACOS; and (3) to determine the need for initial treatment and/or referral. The following is a brief introduction and review of the main elements of the guideline, together with the relevant literature, on the management of ACOS.
I. Background of the Joint Guidelines
In children and young adults, the differential diagnosis of respiratory symptoms is different from that of older adults. Once infectious and non-pulmonary diseases (e.g., congenital heart disease, vocal cord abnormalities) are excluded, the most likely chronic airway disease in children is asthma. In adults (usually after 40 years of age), chronic obstructive pulmonary disease becomes more common, and at this age, the differentiation of asthma with chronic airflow limitation from chronic obstructive pulmonary disease becomes an important issue. Some of the patients with chronic airway disease have features of both asthma and LBP. There is no universally accepted terminology or defining characteristics for this category of chronic airflow limitation. It has been found that patients with both asthma and chronic obstructive pulmonary disease have more frequent exacerbations, poorer quality of life, faster decline in lung function, higher mortality rates, and greater medical costs.
In these reports, the proportion of patients with both asthma and COPD ranged from 15% to 55%, depending on the inclusion criteria used and the age and gender of the patients; 15% to 20% of patients had both asthma and COPD diagnosed by their physicians.
The GINA and GOLD scientific committees noted that the joint guidelines are intended to provide clinicians with a method (measure) to differentiate between asthma, lung disease, and the overlap between asthma and lung disease, and proposed the term ACOS. The joint guideline will describe the characteristics of ACOS and make diagnostic recommendations, giving equal weight to the characteristics of asthma and COPD. In addition, the joint guideline proposes a simple procedure for the initial management of ACOS; its main goal is to guide clinical practice.
Definition
The joint guidelines provide a clinical description of ACOS based on the respective definitions of asthma and LBP, as shown in Table 1.2 The typical features of asthma, LBP, and ACOS are listed in Table 2, showing similarities and differences in history and examination.
Step-by-step diagnosis of patients with respiratory symptoms
The joint guideline proposes a stepwise approach (stepwiseapproach) for the diagnosis and differential diagnosis of asthma, COPD, and ACOS, which is divided into 5 steps, including experimental treatment.
Step 1: Does the patient have chronic airway disease?
The first step in diagnosing this type of disease is to identify patients who are at risk or likely to develop chronic airway disease, and to exclude other possible causes of respiratory symptoms. This is based on a detailed history, physical examination, and other tests (e.g., chest x-ray, questionnaires).
In terms of clinical history, features suggestive of chronic airway disease include:
(1) chronic or recurrent cough, sputum, dyspnea or wheezing, or recurrent acute lower respiratory tract infections;
(2) History of asthma or chronic obstructive pulmonary disease as diagnosed by a previous physician;
(3) History of treatment with inhaled medications;
(4) History of cigarette smoking;
(5) History of exposure to occupational hazards.
Step 2: Clinical syndromic diagnosis of asthma, COPD and ACOS in adults
The joint guideline proposes a diagnostic approach that focuses on the most useful features to distinguish asthma from LBP, taking into account the degree of overlap between asthma and LBP features (Table 2a).
(1) Collecting features that support a diagnosis of asthma or COPD: Features that support a diagnosis of asthma or COPD can be obtained through careful history taking, including age, symptoms (especially onset and progression of variability, seasonality or periodicity, persistence), past history, social and occupational risk factors including smoking history, past diagnosis and treatment, and response to treatment. The small boxes in Table 2b can be used to identify the characteristics that are most consistent with asthma and/or COPD (ticked). It is important to note that the table does not include all characteristics of asthma and LBP, but only those that most easily distinguish between asthma and LBP.
(2) Comparing entries that support a diagnosis of asthma or LBP: Counting the number of boxes checked in each column from Table 2b, if more than one (3) of these characteristics (asthma or LBP) are present, the likelihood of an accurate diagnosis is high in the absence of another diagnostic characteristic. It is important to note that the absence of these features has a low predictive value and does not exclude either asthma or COPD. For example, a history of allergic reactions increases the likelihood that the respiratory symptoms are due to asthma, but is not necessary for a diagnosis of asthma because nonallergic asthma is the accepted phenotype of asthma; and allergic reactions are common in the general population, including patients who later develop slow-onset obstructive pulmonary disease. The diagnosis of ACOS should be considered when a patient has a similar number of features of asthma and lung disease.
(3) Consider the certainty of the diagnosis of asthma or lung disease, or whether the presence of both features suggests ACOS.
Step 3: Pulmonary Function Measurements
Pulmonary function measurements can confirm the presence of chronic airflow limitation, but are of limited value in distinguishing asthma, COPD, and ACOS with fixed airflow obstruction (Table 3).
Although peak expiratory flow rate (PEF) measurements are not a substitute for spirometry and may confirm the diagnosis of asthma by showing excessive variability if the same instrument is used repeatedly for 1 to 2 weeks, a normal PEF does not exclude asthma or lung obstruction. High variability in spirometry is also seen in ACOS.
The provisional diagnosis made in step 2 above needs to be reviewed and revised if necessary after pulmonary function and other test results are available. As shown in Table 3, pulmonary function measured at a single visit is not always conclusive for diagnosis, and the results must be considered in the context of the clinical presentation and whether treatment has been received. Inhaled glucocorticoids (ICS) and long-acting β2 agonists (LABA) can affect pulmonary function measurements, especially if they are not discontinued before or for a short period of time. Therefore, a review of lung function is necessary both to confirm the diagnosis and to assess responsiveness to initial therapy.
Step 4: Initiate initial therapy
When faced with a diagnosis such as ACOS, where asthma and COPD are equally weighted, the “default position” should be to start treatment based on asthma. This is primarily because ICS has a key role in preventing disability and even death in patients with uncontrolled asthma; in such patients, even seemingly “mild” symptoms (compared with those of moderate or severe COPD) may indicate a risk of life-threatening exacerbations.
(1) When a comprehensive clinical evaluation suggests that a diagnosis of asthma or ACOS, or of COPD, is unlikely, it is prudent to initiate treatment for asthma until further testing confirms or rejects this initial diagnosis. It is important to note that LABA should not be used without ICS (so-called LABA monotherapy) if asthma features are present.
(2) If a comprehensive clinical evaluation suggests slow obstruction, appropriate bronchodilators (alone or in combination) should be given for symptomatic treatment, but not ICS alone (i.e., ICS monotherapy).
(3) Treatment of ACOS should also include other strategies and recommendations recommended by the guidelines, including smoking cessation, pulmonary rehabilitation, vaccination, and treatment of comorbidities.
The joint guidelines state that for most patients, the initial management of asthma and COPD can be well implemented in primary care settings. However, both GINA and GOLD provide provisions for referral when appropriate in the management of patients; this may be particularly important in patients with suspected ACOS.
Step 5: Referral for specialized testing (if necessary)
Referral for specialist advice and further diagnostic evaluation is necessary when a patient presents with the following conditions
(1) Persistent symptoms and/or acute exacerbations despite treatment.
(2) There is diagnostic uncertainty, especially if another diagnosis needs to be excluded, such as bronchiectasis, post-tubercular scarring, bronchiectasis, pulmonary fibrosis, pulmonary hypertension, cardiovascular disease, and other causes of respiratory symptoms.
( 3) The presence of atypical signs and symptoms in patients with suspected asthma or lung obstruction may suggest a diagnosis of other lung disease. These signs and symptoms include hemoptysis, significant weight loss, night sweats, fever, and signs of bronchiectasis or other structural lung disease. This condition should be referred as soon as possible without waiting for experimental treatment of asthma or chronic obstructive pulmonary disease.
( 4) Suspected chronic airway disease, but lacking the combined clinical features of asthma and COPD.
( 5) The presence of comorbidities that may interfere with the evaluation and management of airway disease.
( 6) Problems in the management of asthma, COPD and ACOS should also be referred.
Specialized tests that can be used to differentiate asthma from LBP are listed in Table 4.
The recommendations of the joint guidelines for the management of ACOS are presented above. However, it can be seen that the treatment recommendations for ACOS are not yet exhaustive, probably due to the lack of evidence-based medical evidence. To date, clinical trials of medications for either COPD or asthma have not included such “cases where asthma or COPD is not clear”, and therefore there is little mention in the literature on the treatment of ACOS.
Recently, some academic groups have proposed empirical or consensus treatments for ACOS. For example, the Spanish guideline for chronic obstructive pulmonary disease, in its “Recommendations for treatment based on clinical phenotype”, suggests that the basic treatment for the “overlapping phenotype of chronic obstructive pulmonary disease-asthma” is ICS combined with long-acting bronchodilators. Two years ago, the author made reference to GINA and GOLD recommendations for the treatment of asthma and chronic obstructive pulmonary disease, and combined them with relevant research advances to present the main points of the treatment of ACOS (Table 5) for discussion by colleagues.
Obviously, although the drugs used in the treatment of ACOS are the same as those used for asthma and COPD, the principles are different. For example, for long-term treatment, long-acting bronchodilators (β2 agonists and/or anticholinergics) can be used alone in patients with chronic obstructive pulmonary disease, and ICS can be used alone in patients with asthma, but in principle, patients with ACOS should be treated with a combination of ICS and long-acting bronchodilators. It is important to note that all the items listed in Table 5 are essential and cannot be exhaustive. For example, the immediate goals of chronic obstructive pulmonary therapy include not only symptom relief, but also improvement of quality of life and reduction of acute exacerbations, etc. For details, please refer to the original guidelines.