Occupational asthma (OA) is a disease characterized by variable airflow obstruction and/or bronchial hyperactivity due to causes and conditions attributable to a particular occupational environment and not to any other factors out of the workplace [1, 2]. Epidemiological and clinical evidence indicates that multiple agents inhaled at work can induce asthma (more than 300 according to current knowledge) [3, 4]. Table 1 shows the relationship between the principal agents inhaled and the workers with potential risk of developing occupational asthma.

According to the pathogenic mechanism, we can distinguish three types of OA [1, 2, 5, 6]:

1. Immunological OA. This appears after a latency period during which the individual does not yet respond to the causal agent. This may be either a substance of high molecular weight such as latex, enzymes, cereals and flours (typically, involving an IgE-mediated mechanism) or a substance of low molecular weight such as diisocyanates, metals, wood dusts or cleaning agents (in which case the existence of an IgE-mediated mechanism usually cannot be displayed).
2. Non-immunological OA. This is due to a toxic or irritating device. The best-studied form is the Reactive Airways Dysfunction Syndrome (RADS), due to high-dose exposure to an irritant agent that causes the onset of the symptoms within 24 hours. Chlorine, sulfur dioxide, ammonia and combustion products are the most common agents that can induce non-immunological OA.
3. Other forms of OA. This includes forms of OA with special and distinctive features such as asthma-like disorders or the asthma of aluminum producers.

Nonetheless, OA, is part of a wider concept, namely work-related asthma (WRA) [1, 3], which includes work-aggravated asthma, characterized by a pre-existing or concurrent asthma disorder that is aggravated by work conditions and may be difficult to differentiate from actual occupational asthma.

OA is the most frequent respiratory occupational disease in industrialized countries [7]. The data on prevalence vary according to country, the specific population, the different designs of the epidemiological studies, and the definition of OA [2]. According to most studies [8], occupational asthma accounts for between 5% and 25% of asthmatic patients. A recent review study [9] estimated that the average attributable risk is 15%. Considering that asthma affects, on average, 5-10% of the European adult population (about 5% in Spain) with a tendency to increase [10, 11], we are looking at a significant public health problem.

The correct and early diagnosis of OA is of great prognostic, preventive and socio-economic significance. Many different studies show that the sooner the medical treatment is established and the contact with the causative agent is avoided, the better the patient’s prognosis is. However, the diagnosis of a new case of OA requires investigation on behalf of the employee’s company with the aim to elucidate the causative agent and implement the necessary preventive and corrective measures (substitution of products, reduction of exposure, change of the workplace, use of collective and individual protection equipment, etc.) to improve the working conditions not only in the affected patient’s workplace, but also in all similar places or for workers with similar exposures. This would prevent new cases (primary prevention).

To ensure proper primary prevention, cases must be correctly diagnosed. One of the main problems of occupational health in our country is that most occupational diseases are not diagnosed as such in the specialized occupational health services system (work-place accidents and occupational diseases insurance companies or the company prevention services). They are, in fact, diagnosed and treated at the Catalan Public Health Institute (Institut Català de la Salut, ICS) and, thus, are classified as common and not occupational diseases. Respiratory diseases and, specifically, OA are no exception. The MOR (Occupational Respiratory Diseases) [12] platform was created in Catalonia in 2002 to fill this gap; created by volunteer doctors (pneumologists, occupational medicine specialists, allergists and others) who collected a total of 174 cases of OA. During the same period, the official statistics on occupational diseases [13] only registered 42 cases of OA.

Many occupational asthmatics are treated in the Primary Healthcare system, either because they went there on their own initiative or because they were incorrectly referred from the occupational insurance companies. This fact has many negative consequences. Firstly, it is detrimental for the affected workers because even if they are following medical treatment, they continue to be exposed to the causative agent, and may become chronic patients and lose their capacity to work. Secondly, this is to the detriment of other workers performing similar tasks and with similar exposures as the employer does not take any preventive measures. Thirdly, this implies a clear dysfunction between the occupational healthcare system and the public health service, especially the Primary Healthcare system, due to the inappropriate and unjustified transfer of patients. The cost of treating and caring for these patients is borne, to a great extent, by the Primary Healthcare system.

The OA diagnosis consists of two phases. In the first phase, the asthma diagnosis has to be confirmed and in the second phase, asthma has to be associated with the work environment area and the occupational exposures.

1. Asthma diagnosis: The most relevant guidelines in our area, such as the British Guideline on the Management of Asthma [14] from the British Thoracic Society (BTS), the Global Strategy for Asthma Management and Prevention of the Global Initiative for Asthma [15] (GINA) and the Guía Española para el manejo del Asma [16] (GEMA) agree in stating that asthma symptoms, even if they are characteristic, are also non-specific and cannot constitute a diagnosis for the disease leading to the recommendation to perform an objective test that proves a reversible airflow obstruction. The GEMA proposes the application of a sequential algorithm in the Primary Healthcare system. This algorithm is based on clinical tests, pulmonary function and allergic sensitization.
2. Connection with the workplace (occupational asthma diagnosis): the establishment of the connection between asthma symptoms and occupational exposure may be established according to different levels of evidence, depending on the purpose and the circumstances. The OA individual clinical diagnosis requires the highest level of evidence and, in some cases, an absolutely confirmed diagnosis taking into account the medical, socio-economic and legal implications that it may imply. This leads to diagnosis algorithms that are very expensive, risky and not very affordable, with analysis such as the specific bronchial provocation testing that have to be performed in very specialized laboratories, which are not available in the Primary Healthcare system. In both the health surveillance programs and in the epidemiological studies, the requirements are less strict and they aim to establish the link between the symptoms and the occupational exposure without the need to carry out very complex or expensive tests.

This study aims to estimate the prevalence of occupational asthma and asthma aggravated by working conditions among patients diagnosed with asthma as well as to discover the real impact on the Primary Health care system caused by under-diagnosis and inappropriate referral of OA.

This knowledge is necessary to take corrective action and achieve the ultimate goal: improving health and occupational prognosis of patients with OA and to improve risk prevention in companies avoiding the appearance of new cases.

Considering that the aim of the study is to identify a group (patients with OA) to evaluate the magnitude of the problem in the Primary Healthcare system, the specific confirmation of individual cases is not as essential as the global vision of the problem. This is why, following the criteria of organizations and expert groups (American College of Chest Physicians, ACCP; Sentinel Event Notification System for Occupational Risk, SENSOR) [1,17], we have established the link between the clinical chronology and work environment as a basis for the diagnosis of OA in the design plan for the study, considering the clinical and occupational history of the patient at all times [18].

From an ethical point of view, the study will identify the OA patients who were classified as having common asthma and will allow refer them to the appropriate service (occupational health services or other labor-related insurance companies) with the benefits that this may bring to the patient from a preventive, prognostic, legal and an economic point of view (recognition of an occupational disease).

A very important bias in the asthma diagnosis is the clinical similarity to chronic obstructive pulmonary disease (COPD). On the one hand, there are patients diagnosed with COPD who are, in fact, asthmatic. There are also cases of patients who are smokers where COPD and asthma co-exist. According to the GEMA guideline and the differential diagnosis table included within, the present study will include, in the first stage of the screening, COPD diagnosed patients. But patients with COPD are not included in the sample; we review the clinical cases in which this diagnose is not clear whether it was COPD or asthma, and once confirmed that was not COPD, the case was included in the sample.

The results obtained can have a prominent epidemiological and welfare impact. From an epidemiological perspective, occupational asthma ethiology is not usually evaluated, neither is the deterioration that the work environment can cause to asthmatic patients. From a medical-care point of view, this can imply a poor level of control of the disease, a higher economic cost and a very significant medical burden.

We consider that despite the evidence that many occupational agents can induce asthma or significantly aggravate preexisting asthma, this issue is not usually investigated in the day to day practice [19], and therefore we do not have any objective data to quantify this fact.

Given the fact that the geographical environment of this study is very diverse (from rural areas to highly industrialized regions), we believe that this is a good territorial model to extract prevalence data that can be generalized. On the other hand, considering that in Catalonia the health system is homogeneous, results on the OA cost will be extrapolated. Thanks to the employment questionnaire, the workplaces presenting the highest risk of developing asthma or that make pre-existing asthma become worse and out of control are expected to be detected. We will also have more objective data that will allow us to advise the patients about the risk of certain work environments and the preventive measures to take.

In Catalonia, this is an issue of particular interest, taking into account the lines set out in the current Health Plan, which considers as key issues both the improvement in the detection and the declaration of occupational diseases treated in the Primary Healthcare section of the public health system and the establishment of recommendations for prevention and control.

Occupational health services are quite heterogeneous depending on country. However, primary health care or general medicine tends to be at the heart of the initial suspicion of work-related asthma. For example, when establishing the asthma diagnosis in adult patients, primary health care physicians should always consider the potential work-related origin of the illness and should carry out the proper anamnesis of their labor background [20]. Therefore, we feel that the results of this study may be of interest, given that they reinforce the idea that many asthma cases are diagnosed and treated in primary health care consultations and that not all are derived from the occupational health care centers. We believe that this is not a situation that is unique to Catalonia but rather, that it is common across the Spanish National Health System and, by extension, to all countries that organize their healthcare services based on regulatory (gatekeeper) access to a universal healthcare system for the general population. On the other hand, we also feel that it may be extended to those systems in which the healthcare and the occupational healthcare networks are not fully integrated.

The project results will be easily applied and may be extended to all the Primary Healthcare services. Furthermore, in the event of achieving the objectives of the study, we expect to rationalize or reduce costs and improve in efficiency.

We believe that the study design is of interest from an epidemiological point of view since we propose the study of the health problem on a population basis (265,000 inhabitants in a defined area). This design also allows us to determine the diagnostic appropriateness of asthma as all of the diagnoses shall be reviewed by medical experts. Furthermore, there are very few studies on the prevalence of work-related asthma that offer a breakdown of the impact of assistance on primary healthcare services. We also feel that the diffusion and publication of the research protocol facilitates its evaluation, allowing the study to be included in future systematic reviews [21] and offering transparency to the research process as it offers a clear description of the procedures followed, making its reproduction possible in other situations

The project will be presented to the patient during his/her first appointment with the Primary Healthcare professional. The doctor will distribute an information sheet about the study and an informed consent form and will ask for the patient’s permission for his/her voluntary participation.

The informed consent form will contain the terms of the general and particular ethical conditions regarding his/her privacy, anonymity, confidentiality rights (therefore, only the researchers and monitors/auditors will have access to the data of the participating subjects), cancellation and information rights.

The researchers agree to comply with the current rules of Good Clinical Practice and the applicable requirements of the Declaration of Helsinki. For this reason, we will use a 7-digit code for the identification of each patient: the two first digits will identify the centre, the two following ones the professional responsible for the evaluation, and the last three digits will correspond to the patient, in order of entry into the study. The benefits for the patients participating in this study are the following: the possibility of establishing a correct diagnosis of their asthma disease and its association with their work environment. We will explain the subjects that this study is completely confidential and that their employment company will not be informed about this without his/her explicit consent.

This study was approved by the Ethics Committee of Clinical Research in Primary Care Research Institute Jordi Gol (Barcelona, Spain).

APPENDIX.