Although asthma and chronic obstructive pulmonary disease (COPD) are considered distinct obstructive airway diseases, the coexistence of features of both diseases in the same patient has been long recognized. In this context, the individualization of an entity of overlap between asthma and COPD has recently been proposed. Several publications from diverse working groups have proposed different terms and classification criteria to describe these patients.1–7 However, none of these terms or criteria has been universally accepted.

The lack of consensus on how to define and categorize such an entity of overlap between asthma and COPD limits the development of prospective studies needed to determine the optimal approach to these patients.

Some authors have already published a diverse set of criteria for asthma/COPD overlap. Most can be grouped by category, such as (1) clinical criteria and related risk factors, (2) lung function and (3) laboratory data/immune-inflammatory markers. Among the proposed criteria are: (1) simultaneous presence of clinical features of asthma and COPD in the same patient, previous history of asthma or atopy, current or past history of smoking or biomass combustion exposure, age >40 years-old; (2) presence of persistent airflow limitation (post-bronchodilator FEV1/FVC<0.7), positive or very positive response to the bronchodilator test (FEV1 increase of at least 200mL and 12% or at least 400mL and 15%, respectively), presence of bronchial hyperresponsiveness; (3) peripheral eosinophilia (>300eosinophils/μL or >5% of the total leukocytes), sputum eosinophilia, elevation of the fractional exhaled nitric oxide (FENO) and elevation of total serum immunoglobulin E (total IgE).1–7 In fact, our group carried out a review of the main definitions and diagnostic criteria which was published recently,8 in addition, in this paper a proposal of recommendations adapted to the Portuguese situation was achieved by a group of respiratory disease experts. In order to obtain a broader consensus, a larger study was needed, leading to the present project.

The main aims of this project, intended to be adapted and applied in Portuguese clinical practice, were:

• 1.

  to assess the need for the recognition of an overlap entity between asthma and COPD within the Portuguese medical community who treat patients with respiratory diseases;

• 2.

  to achieve consensus over terminology and classification criteria for such an entity;

• 3.

  to achieve consensus on the approach and adequate orientation of these patients.

This study was conducted by a multidisciplinary panel of experts from three distinct medical specialties: Pulmonology, Family Medicine and Immunoallergology.

A committee panel was created with elements from the three specialties described above. This committee selected a total of 190 members from the three medical specialties – Pulmonology (n=85), Family Medicine (n=62) and Immunoallergology (n=43) – to participate in the questionnaires based on their expertise in obstructive airway diseases.

The study followed a Delphi structure with three rounds of questionnaires. The first questionnaire was mainly composed of open-ended questions in order to obtain meaningful answers that reflect the overall non-conditioned opinion of the participants. A classical content analysis was endorsed, organized by tabulating records with the frequency of freely elicited ideas. The results were discussed within the scientific board of a multidisciplinary panel of experts and the subsequent survey was drawn up based on the answers obtained in the first round, the same process was used for the final questionnaire. The second questionnaire was intended to be the cornerstone of the inquiry, containing a detailed and wide range of questions comprising nomenclature and the three main domains of the diagnostic criteria (clinical, lung function and laboratory data/immune-inflammatory markers), as well as treatment approach and orientation of the patients. The third questionnaire aimed at clarifying any topic that had not been fully established in the preceding round or any doubt that had arisen in the discussion of the data obtained previously.

The answers were not conditioned in any way, even if only theoretically. Previously existing ideas and concepts were on the basis of this consensus survey.

These questionnaires were inserted into an online platform specifically created for this study. A link to this platform was sent via electronic mail to the clinicians who answered anonymously and with a user sensitive and confidential password to provide access to the platform. The clinicians were allowed to answer each questionnaire in stages; they did not need to answer everything at once. Answering time ranged from minutes to two weeks, so that the participants had enough time to think about their answers, which did not force a pattern of only immediate opinions.

After the application of the questionnaires, a final meeting took place, involving the committee panel and some of the respiratory experts that had participated in this study, in which the results were discussed and a consensus was obtained in terms of classification criteria, treatment and orientation of ACO.

Each step of the Delphi had a different number of responders, the first questionnaire having the lowest participation (Table 1).

This study was the first to explore the concept of asthma-COPD overlap within the Portuguese medical community, enabling a consensus regarding the need for the recognition of an overlap entity. A significant number of participants and the use of a Delphi method strengthened the study results. After a final meeting, where all the results were discussed, it was possible to reach a consensus over nomenclature, classification criteria, treatment and orientation of these patients.

The existence of patients who have at the same time clinical characteristics of both asthma and COPD has been a well-known fact for many decades,9,10 but only recently has it begun to attract more attention.1–8 The need to define this entity is something that is shared by most clinicians who work in respiratory medicine. In our study, the majority of the respondents to the first questionnaire (87.2%) confirmed this intention. However, there is still a lack of clear and solid diagnostic criteria for this overlap which can be used by all clinicians, an idea shared by most in our study group (85.1%).

There have been a few guidelines, published in recent years, proposing specific criteria for the diagnosis of the asthma-COPD overlap entity. The first was created by the Spanish group GesPOC in 2012,1 followed by the Finnish2 and Czech guidelines3 with similar proposals. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) and the Global Initiative for Asthma (GINA) published a joint document in 2014.4 A more recent consensus between specialists from North America, Asia and Europe was also published.5

Although very recently a Portuguese meeting of experts in respiratory medicine produced diagnostic recommendations for ACOS,8 there was a need for a broader analysis using a more accurate method for assessing the perspective of the Portuguese medical society on the asthma-COPD overlap, by recruiting a considerable number of clinicians in three fields of Medicine (Immunoallergology, Family Medicine and Pulmonology).

The designation of the overlap entity was one of the points addressed in the first questionnaire. Most of the clinicians chose between two of the most commonly accepted names – asthma-COPD overlap syndrome (ACOS) and asthma-COPD overlap (ACO). Since the overlap between these two chronic lung diseases is not really a syndrome or a single disease, we believe that ACO should be the chosen designation, which is in line with what is recommended by the latest GOLD and GINA joint guideline on ACO.6

We can divide the diagnostic criteria into three main categories: Clinical, Lung function and Laboratory data/immune-inflammatory markers.

In terms of clinical criteria, the presence of simultaneous clinical characteristics of asthma and COPD in the same patient was considered highly relevant and should be listed, according to the majority of the clinicians, as a major diagnostic criterion. This is in line with what is sustained in several guidelines, such as the Spanish, Finnish and Czech, although with some slight differences in some of them. Also seen in most guidelines is the presence of a previous history of asthma and smoking history/exposure to biomass fuel combustion, which were also considered relevant criteria in this survey.

One of the main concerns in clinical practice is to identify which COPD patient would benefit from the use of ICS. This is where the algorithm for ACO can play a role, and so it seems more important that we have a diagnosis of COPD in a patient that may also have a diagnosis of asthma or have evidence of positivity on bronchodilation tests. The need for having a COPD diagnosis is stated in a recent GesPOC and GEMA algorithm.7 However, this diagnostic approach was not assessed in our study, so we cannot comment on what the clinician's opinion would be on this.

On the other hand, other criteria such as a previous history of atopy and age ≥40 years were considered as minor criteria.

Regarding lung function, almost all clinicians agreed that the presence of a fixed airflow obstruction (FEV1/FVC<0.7) is highly relevant for the diagnosis of ACO and should be considered as a major criterion. This criterion is also present in most of the guidelines. There is more heterogeneity in terms of bronchodilation test positivity. In our Delphi, a positive bronchodilation test, with an increase in FEV1 of at least 200mL and 12%, and a positive bronchodilation test on more than one occasion were considered highly relevant and major criteria. A very positive bronchodilation test, with an increase in FEV1 of 400mL and at least 15%, was not considered as relevant, contrary to several guidelines, where this is listed as a major criterion.1–3 By lowering the threshold for the bronchodilation criteria we risk over diagnosing COPD patients with ACO, and so it is important to register the maintenance of these results on more than one occasion for a more accurate ACO diagnosis. Although we might have a more “definitive diagnosis” of ACO with a very positive bronchodilation test, we might be missing some patients who could benefit from the use of ICS.

In terms of laboratory data/immune-inflammatory markers, the participants in our study did not consider any of them as highly relevant or as major criteria. Peripheral eosinophilia, defined as >300 eosinophils/μL or >5% of leukocytes, and elevation of specific IgEs or positive skin tests for common allergens, were the criteria that received most consensus (>70% of the participants agreeing with their inclusion) and should be considered as minor criteria. Some guidelines considered the inclusion of an elevation of total IgE and FENO as diagnostic criteria of ACO in a COPD patient. FENO is an immune-inflammatory marker of increasing importance and application, but the lack of established cut-offs justifies the decision not to include this criterion in the diagnostic algorithm. Also, the fact that it is not widely available in many clinical settings limits its applicability. However, in some cases, it might be taken into account in order to help support the diagnosis.

The clinicians in our study considered a minimum of 2 major and one minor criteria for the diagnosis of ACO. In most guidelines, the presence of a least 2 major or 2 minor and 1 major is considered sufficient.

The definition of an algorithm for the diagnosis of ACO was established after the final meeting of respiratory experts. It was assumed that this diagnosis should only be considered in patients that have “simultaneous clinical characteristics of asthma and COPD” and “fixed airflow obstruction (FEV1/FVC<0.7)”. As a result, these two criteria must always be present and do not count as major criteria. The diagnostic algorithm can be seen in Fig. 1. The proposed criteria for establishing the diagnosis of ACO are listed in Table 2.

Figure 1.

Algorithm for the diagnosis of ACO.

(0.05MB).

Concerning treatment, most clinicians agreed that ACO should have a specific therapeutic approach. The combination of ICS with LABA or LAMA was considered the first line of treatment by the majority, and the use of triple therapy with ICS plus LABA and LAMA in more severe or symptomatic cases (Table 3). Although there is still a lack of scientific evidence to support these choices, there seems to be some consensus on this subject with the use of ICS plus LABA or triple therapy being recommended by the majority of the guidelines.1–8 The use of ICS plus LAMA was also considered as a valid first-line therapeutic option by a considerable number of clinicians. This differs from what is recommended by most consensus documents1–8 but could be a plausible choice and should be the subject of future interventional studies on ACO patients.

Non-pharmacological treatment also plays a very important role in ACO patients and this was stressed by the clinicians in this study. Smoking cessation, pulmonary rehabilitation, pneumococcal and influenza vaccination, reinforcement of the therapeutic adhesion, verification of the inhalation technique and comorbidities treatment were considered key components in the management of these patients. The importance of these measures has a very high consensus in the medical community and is present in most guidelines, not only for ACO but also for COPD or asthma.

The place for initial assessment and clinical orientation of ACO patients was also evaluated in this study. Clinician's answers were divided between a specialist hospital clinic and primary healthcare on the subject of initial diagnostic medical approach and follow-up. The latter option was mainly considered by Family Medicine specialists, which might be a bias since the majority of them had a clinical focus on chronic airway diseases and might not correspond to the overall reality of Family Medicine practice in Portugal. Moreover, in settings with a lack of diagnostic resources, there might be a more consensual need for a hospital referral. Additionally, we believe that a patient with a symptomatic or severe ACO should also be referred to a specialist. Although there is no established definition on what constitutes severe ACO, we suggest following the national recommendations for hospital referral in asthma and COPD patients.11,12 Regarding the periodicity of clinical and lung function evaluation, according to the majority of the clinicians, it should be performed every 3–6 months in the early phase, and then adapted to the patient's clinical severity and symptoms.

This Delphi survey is the first one to analyze the opinion on asthma/COPD overlap of the Portuguese medical community. The fact that we have clinicians from different medical specialties, who manage patients with respiratory conditions, enables us to have a broader understanding of this entity. This is also one of the largest studies, in terms of number of participants, on this subject, which strengthens the relevance of the results. The use of a Delphi methodology also enabled to access the different items more accurately, in a step by step approach.

The fact that we had a rather low participation in the first questionnaire, probably because of its open ended based questions, and the lack of mandatory consecutive answers to all the questionnaires, are weaknesses of this study.

Asthma-COPD overlap has been a matter of interest and debate in the last few years. Different criteria and diagnostic algorithms were proposed for establishing the diagnosis of ACO. However, there is a lack of consensus regarding this issue. This study had a nationwide participation of clinicians from different medical specialties that manage patients with chronic obstructive airways diseases. It was clear that the information previously available regarding this entity was not sufficient for their daily clinical practice and there was a general agreement about the need to define ACO. Based on the Delphi method, sequential steps of a set of questionnaires were applied and analyzed in order to establish diagnostic criteria and an algorithm for the approach of ACO, adapted to our national context.

The authors have no conflicts of interest to declare.