AIMAR survey on complex forms of bronchial asthma and COPD, their management and perception of critical issues
© Donner and Visconti; licensee BioMed Central Ltd. 2014
Received: 27 August 2014
Accepted: 24 September 2014
Published: 28 October 2014
The management of patients with complex forms of bronchial asthma and COPD is not usually addressed in the major international guidelines and management documents which exclusively address pure forms. AIMAR thus undertook a survey to obtain information about: a) the perceived frequency of complex forms of asthma/COPD in adult patients and in the elderly; b) patient management regarding the complex forms (focus on therapeutic goals and consequent treatment); c) the management problems perceived in diagnosis, management, monitoring, indices of appropriateness in pharmacological treatment and adherence to treatment.
The survey consisted of 18 multiple choice questions, completed by means of a web-based electronic form published in internet. All the data and responses inserted in the system were checked on-line for coherence and completeness directly during the phase of insertion and each participant had one only possibility of participating. The data thus collected were memorized directly within a relational database, based on consolidated open-source MySQL technology, and thus were immediately available for examination also during the course of the survey. Access to the data, mediated by a “back office” system of interrogation and report, enabled constant monitoring of the survey as it was being carried out, as well as extractions and verification, even on smaller data sets.
The survey was carried out in the full month of December 2013 and first half of January 2014. A total of 252 questionnaires were collected from the following physician groups: pneumologists (n = 180), general practitioners (GPs) (n = 32), allergologists (n = 8), internal medicine specialists (n = 20), other specialists (n = 12).
Complex forms of bronchial asthma and COPD are frequently observed and considered present in variable percentages ranging from about 10% to about 50% of patients visited and considered typical of patients with a previous history of asthma. Risk factors such as smoking, obesity, bronchial hyperreactivity and genetic predisposition are considered important. Diagnosis is difficult solely on the basis of symptoms in approximately 50% of cases, and a previous history of asthma, history of spirometry and presence of allergy are of help. Treating inflammation and reducing exacerbations are considered the key therapeutic goals and the combination of inhaled corticosteroid (ICS) and long acting β2-agonist (LABA) and monotherapy with ICS are considered the fundamental pharmacological mode for treating patients with mixed forms of bronchial asthma and COPD. Treating with only a bronchodilator is considered to be moderately risky for this type of patient. The identification and management of mixed forms result more impeded by “logistic” aspects, e.g. long waiting lists and integration with the GP, than by aspects intrinsic to the disease management itself, e.g. selecting the assessment or interpreting the outcome of the instrumental examinations. Treatment continuity and the integration between GP and specialist are the factors that most limit the management of mixed forms in the stable phase.
Bronchial asthma and chronic obstructive pulmonary disease (COPD) are chronic diseases that are very widespread and are characterized by an increasing epidemiological trend. It is estimated that asthma affects about 4% of the adult population and 9-13% of the pediatric population in developed countries, including Italy. COPD affects approximately 5% of the general population, is concentrated in the adult and elderly age-ranges, and the prevalence can reach rates of even over 20% in the subgroup of males aged over 60 years .
Both diseases are characterized by the presence, with diverse features, of airways inflammation and airways obstruction, with respiratory symptoms that are often in part identical. They are, however, two clearly distinct diseases, with specific pathophysiological and clinical characteristics that sharply differentiate them. But cases are not infrequent of single patients, particularly amongst the elderly, in whom it is difficult to make a differential diagnosis due to “complex” syndromes where asthma and COPD overlap in the same patient, such as can occur, for example, in an asthmatic individual exposed to inhalation of harmful substances, like cigarette smoke. The diagnosis and management of such patients are unfortunately not dealt with in the major international guidelines - such as GOLD for COPD and GINA for asthma - that refer to pure forms, completely excluding the complex forms.
Perception of the frequency of complex forms of asthma/COPD in adult and elderly patients;
mode of clinical management of patients with forms characterized by the presence of both components, with particular regard to the therapeutic goals and consequent treatment;
perception of possible difficulties of management in the diagnosis, treatment, monitoring, and evaluation of the indices of appropriateness in pharmacological treatment and of adherence to treatment.
A working group of qualified experts elaborated, on the basis of the above goals, a survey designed to acquire data through a dynamic “form”, always available in internet, able to be completed at any moment by the person concerned, in a few minutes and with a few simple interventions. The categories of specialists to whom the survey was administered were basically three (pneumologists, allergologists, and internal medicine specialists) with extension to general practitioners (GPs). The survey consisted of 18 multiple-choice questions completed by means of a web-based electronic form published in internet - time required for completion of the survey was not more than 15 minutes. All the data and responses inserted in the system were checked on-line for coherence and completeness directly during the phase of insertion and each participant had one only possibility of participating. These measures ensured verification of the data at the survey was being conducted, eliminating cases of partial data and possible duplications due to multiple participation (which would obviously have lowered the significance of the final results).
The data thus collected were memorized directly in a relational database (based on the consolidated open-source technology MySQL, a de facto standard in web applications) and thus were immediately available to examination also during the period while the survey was being conducted. Access to the data, mediated by a “back office” system of interrogation and report, enabled constant monitoring of the survey as it was being carried out, as well as extractions and verification, even on smaller data sets.
The survey was carried out during the full month of December 2013 and first half of January 2014: in this period a total of 252 physicians responded to the survey; they were distributed among the above-mentioned categories that took part, thus enabling a heterogeneous and interdisciplinary overview of the topic under investigation. The enrollment of participants highlighted the positive synergy between “web-based” technologies  and the social networks [2, 3] alongside the normal, classic system of invitation to participate carried out by bulk mailing. The initiative was promoted at several occasions through the social network channels where AIMAR has for some time been present. Through its own page in Facebook (institutional group profile  and official Twitter channel ), it was possible to reach rapidly a large number of heterogeneous participants spread throughout the national territory (confirming once again the “viral” effect of the social networks in involving people and circulating information).
Results and discussion
Overall 252 questionnaires were collected, subdivided into: Pneumologists = 180,GPs = 32, Internal Medicine specialists = 20, Allergologists = 8, other Specialists = 12.
Complex forms of bronchial asthma and COPD are retained typical of patients with a previous history of asthma. It is now known that forms or phenotypes of severe chronic bronchial asthma exist and have similar characteristics to those of COPD, namely: accelerated lung function decline with a progression towards poorly reversible bronchial obstruction, neutrophils in sputum and/or inflammation difficult to control by therapy, elevated level of bronchial hyperreactivity, and frequent exacerbations [4, 7–10].
The assessment solely of respiratory symptoms (dyspnea, cough, sensation of chest constriction) as well as a single spirometry test do not generally permit to recognize a form in which bronchial asthma and COPD overlap. In fact, as reported above, there are cases of asthma (of long duration, in smokers or the elderly) with poor or even absent reversibility, and, viceversa, cases of COPD with a certain amount, even significant, of reversibility, perhaps due to the coexistence of an asthmatic component.
The diagnostic establishment of “complex” forms of asthma and COPD is thus difficult and must take into account the overall assessment of the patient based on an in-depth clinical-anamnestic examination: type and mode of onset of symptoms (association to triggering factors), previous history of atopy or asthma, history of smoking, spirometry data with reversibility, previous episodes of bronchial hyperresponsiveness, clinical signs and x-ray findings.
It should be recalled that also a poorly developed lung at birth, due to nutritional deficits or toxic-infective factors occurring in utero or in the early phases of life, can render the respiratory system more vulnerable to external agents (e.g. smoking, viral infections) and represent a risk factor for the early development of an obstructive condition that is poorly reversible [4, 12].
Finally, both asthma and COPD can be considered the result of a complex interaction of endogenous and exogenous factors. External agents (allergens in asthma and smoking in COPD) presumably act on a terrain that is constitutionally susceptible (genetic predisposition) creating favorable conditions for the initiation of inflammatory and obstructive processes.
It is well known that in eosinophilic asthma the response of the inflammatory and clinical picture to inhaled steroid therapy is excellent: reduction of the cell count, improvement of bronchial hyperreactivity, prevention of exacerbations and improvement of quality of life . However, the recent study GLUCOLD carried out in patients with COPD, excluding those with a current or past history of bronchial asthma, found that long-term treatment with inhaled steroid significantly reduced non eosinophilic bronchial inflammation (mast cells, CD8+ and CD3 + lymphocytes), increased the epithelial integrity and improved the clinical picture . The addition of a beta2- stimulant improved the spirometry indices and dyspnea, even if it did not have an effect on the bronchial inflammation. The specificity of the effects of the steroid has been demonstrated by the observation that its suspension determined a resumption of the inflammatory process and a worsening of symptoms and of spirometry parameters .
The fundamental role of treatment continuity with ICS regimes for attaining the clinical outcomes, both in bronchial asthma and in COPD, is supported by multiple evidence in the literature [14–17]. For example, the COSMIC study has shown that the suspension of inhaled corticosteroid in patients with moderate-severe COPD stabilized with the combined therapy fluticasone/salmeterol led to a rapid and significant deterioration of respiratory function and symptoms, confirming the key role played by this class of drugs as maintenance therapy for COPD .
In line with the opinion that overlapping forms can have an asthmatic origin (or are forms of late onset asthma) and that treating the inflammation together with reducing exacerbations are the principal goals of pharmacological therapy, continuing treatment with ICS, both alone and in association with a LABA, is considered fundamental for the treatment of these patients. However, in contrast with these observations, from the survey it emerged that many physicians do not consider it right to exclude the use of LAMAs or LABAs in monotherapy, considering the use of the bronchodilator alone (without inhaled corticosteroid) only “moderately at risk” (Figure 8). On this point, it should be emphasized that LAMAs are currently indicated only for the treatment of COPD and that the use of LABAs in asthma is subject to precaution: the U.S. Food and Drug Administration has in fact recommended that in asthma LABAs (salmeterol or formoterol) should always be prescribed as additional therapy to inhaled corticosteroids, when the latter alone do not provide an adequate control of symptoms, specifying moreover that, if appropriate, use of a combined LABA-corticosteroid product for inhalation may be preferable to the single components, as means to increasing the compliance to the prescribed treatment .Concerning treatment of the overlapping forms it is important to recall that the major international guidelines address the pure forms (GINA for bronchial asthma and GOLD for COPD). The therapeutic goals of GINA and GOLD have many elements in common (relief of symptoms, prevention and treatment of exacerbations, improvement of the quality of life, good tolerability of the pharmacologic treatments, etc.), but the therapeutic approach is in part reflective (Figure 9): in asthma ICS constitute the driver of the therapy, to which LABA bronchodilators are added to achieve/improve control in patients who are symptomatic with ICS alone, whereas in COPD bronchodilators represent the first step of treatment, to which ICS can be added when indicated (in patients with frequent exacerbations, etc.) in the severe to very severe forms. In forms where asthma and COPD overlap, the combined use of ICS and LABA can be appropriate.
Of the physicians who responded to the survey, most (184 out of 252) retain that there is no standardized pharmacological treatment for COPD patients and that thus this has to be tailored to the individual patient. The net minority (68 out of 252) who retain that there exists a standardized treatment for COPD patients consider prevalently bronchodilators, used either singly (20) or an associated use of bronchodilators (8), as the primary approach as opposed to the association of ICS + bronchodilator (12) or other interventions ( 24) such as, for example, LAMAs or roflumilast.
Critical problems in management
People with an overlap of asthma and COPD, for whom the term “asthma-like bronchitis” was once used, present an inflammatory and obstructive picture that can benefit from early use of the combination of inhaled corticosteroids and long-acting bronchodilators, such as LABAs.
The major elements that emerged from the survey are the following:
The physicians involved in the survey were in general very conservative and prudent in their replies and we had the clear feeling that they were afraid not to give correct or orthodox replies to some critical questions.
Complex forms of bronchial asthma and COPD are considered, by the sample of physicians who took part in the survey, to be present in a variable percentage ranging from about 10% to about 50% of patients visited.
Complex forms are considered to be typical of patients with a previous history of asthma, particularly if smokers.
Risk factors such as smoking, obesity, bronchial hyperreactivity and genetic predisposition are considered to be important for the onset of a complex form of asthma and COPD.
In the majority of cases complex forms of asthma and COPD are difficult to diagnose based on symptoms alone. A previous history of asthma, spirometry records and the presence of allergy are held to be important for the diagnosis.
Reducing the frequency and severity of exacerbations and treating the inflammation are considered to be the principal therapeutic goals for the treatment of the complex forms of bronchial asthma and COPD.
Inhaled corticosteroids (ICS) variously associated to bronchodilators constitute a pharmacological presidium considered fundamental for the treatment of patients with complex forms of bronchial asthma and COPD. Treatment with bronchodilators alone is considered on average at risk of masking the symptoms in this type of patient.
The recognition and management of complex forms is hampered more by technical-administrative difficulties, such as long waiting lists, logistical problems and costs, than by aspects inherent to the management of the disease such as the identification of the most suitable examination and the interpretation of the results of instrumental examinations.
Treatment continuity and the integration between the GP and the specialist are the factors that most limit the management of complex forms of asthma and COPD in the stable phase.
The current guidelines for bronchial asthma and COPD are considered important for the management of the “pure” pathologic forms but less so for the complex forms: in neither document, in fact, is there reference to the diagnosis and management of this type of patient.
The quality and the ease of use of the device are highly important for achieving the therapeutic goals and adherence to therapy.
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