Symptoms and diagnosis

Living with severe asthma is a real challenge!

The countless symptoms and discomfort that affects your family, work and social life, frightening and unpredictable exacerbations, absence from work/school, constant visits to the doctor, side effects from the medication, the inability to carry out daily activities.

You can do better!

Everyone has some sort of illness, and everyone deserves a detailed examination and the best medicines.

Don’t settle for anything less than that!

Asthma is the chronic inflammatory disease of the lower airways that is usually successfully treated with long-term use of disease-control medication (which reduce inflammation) and with the occasional use of medicine that reduces the symptoms.  Some of you have inflammation that is very difficult to treat, which is why symptoms of illness and/or exacerbation are often present.  It can be a sign that you have severe asthma, which is why a detailed examination is necessary to determine the true nature of your disease.

In order for you to understand your illness and to successfully treat it, you must first get to know it well.

Asthma control

Achieving and maintaining good asthma control is the main goal of treatment and a condition for staying in good shape without the disease getting more severe. For doctors, well-controlled asthma means the absence of symptoms during the day as well as at night, without the need for medication for quick relief of discomfort, without restrictions in performing daily activities and without exacerbation. To achieve this, doctors recommend inhaled corticosteroids in different doses with/without other asthma control medication – tailored to each of you individually. In essence, minimal therapy that ensures good/optimum disease control is always what is sought for.

Response to therapy is one of the main indicators of asthma severity. Often the symptoms of the disease disappear soon after the introduction of inhalation therapy, which means that you have a milder form of asthma. But this is not always the case. Sometimes even fully optimized treatment is insufficient and that is when we are talking about severe asthma.

Your asthma is uncontrolled when you have:

– Asthma symptoms (breathlessness, tight chest, coughing) more than twice a week

– The need for medication that quickly eliminate symptoms more than twice a week

– Waking up during the night due to asthma more than twice a month

– Difficulties in performing daily activities

– Two or more exacerbations requiring oral corticosteroids per year or at least one exacerbation requiring hospital treatment the year before

– Impaired lung function determined by spirometry

Difficult-to-treat asthma

Did your doctor recommend a high dose of inhaled corticosteroids in combination with other control medications, and you still have symptoms and exacerbations? Asthma can be difficult to treat if there are triggers that cause symptoms and exacerbations that you are unaware of or have not discovered yet.

Asthma treatment involves the regular use of medications along with the elimination of potential risk factors. If you voluntarily decide to quit inhaler therapy (‘pumps’) because you have eliminated potential risks, or if you do not deal with the risks because you take your medication regularly, there is a good chance that your asthma will remain uncontrolled. Work with your doctor to discover the causes of your symptoms and adjust the treatment of the disease according to your needs.

Are you regularly using the recommended therapy and have dealt with your risk factors the best way you could, but you still have symptoms and exacerbations? It is time to see a doctor specializing in severe asthma!

Risk factors for bad asthma control

– Irregular use of medication for disease control

– Excessive use of medication to relieve symptoms

– Taking medication such as beta blockers and non-steroidal anti-inflammatory medicine (NSAID)

– Bad climatic conditions and microclimate at home or at work

– Domestic animals or pets (in case of hypersensitivity)

– Lifestyle habits (smoking, lack of physical activity, obesity)

– Unknown or untreated associated diseases (comorbidities)

Comorbidities

Comorbidities contribute to asthma symptoms and exacerbations, as well as to poor quality of life. Without their adequate treatment, it is impossible to achieve good asthma control. The most common comorbidities are: nasal polyposis, chronic rhinosinusitis, vocal cord dysfunction, reflux disease, anxiety and depression, obesity, obstructive sleep apnoea, bronchiectasis, heart disease, kyphoscoliosis due to osteoporosis, etc.

Severe asthma

If you have asthma that requires more intensive treatment in order to achieve optimum control of the disease, or despite such treatment your asthma remains uncontrolled, while you also reduce risk factors and treat comorbidities, then you have severe asthma.

Diagnosing severe asthma is only the first step of your treatment. Severe asthma is a heterogenous condition, which means that it has different clinical manifestations:

– the onset of the disease can be in early childhood, adolescence or adulthood

– it can occur with comorbidities or on its own

– symptoms are caused by allergens, viruses, psychological stress or other

– it may begin as a mild asthma or has a severe form from early onset

– the response to inhalation therapy is reduced or entirely absent

– lung function is preserved, declines gradually or suddenly

– there are markers of inflammation of the lower respiratory tract in which eosinophilic cells or neutrophil cells predominate or there are no inflammatory cells or no inflammation at all

The determined specific form of your severe asthma is what doctors call ‘severe asthma phenotype’. In order to determine which form

your asthma belongs to, it is necessary to analyse the blood eosinophils, sputum from the lower respiratory tract with the determination of inflammatory cells, allergies (total IgE and IgE specific, skin prick testing), the presence of chemical compounds in exhaled air (nitrogen monoxide), lung imaging – depending on the history of your illness and your current symptoms. Once the specific form of your severe asthma (phenotype) is determined, your doctor will be able to recommend different treatment options that are reserved only for patients with severe asthma – depending on the phenotype of your disease.

Severe asthma phenotypes

There are two basic categories of severe asthma that are determined by the presence of inflammatory cells in the airways: (i) asthma in which Type-2 (T2) inflammation predominates; (ii) asthma in which there is no Type-2 inflammation (non-T2). These categories are determined based on response to treatment. For example, if your asthma is dominated by T2 inflammation, then a positive response to high doses of inhaled corticosteroids or biological therapy is expected. If you have non-Type-2 inflammation, then the response to inhaled corticosteroids is very weak or completely absent, while biological therapy for this category of severe asthma is still in development and currently unavailable.

Severe asthma with a T2 inflammation

This category of asthma can be divided into subcategories (phenotypes):

1. Severe allergic asthma: its onset is usually in childhood, it is often associated with allergic diseases such as allergic rhinitis and/or atopic dermatitis and allergies in the family. Symptoms occur when exposed to allergens such as dust mites, pollen, pet allergens, etc. Exposure to allergens leads to the production of specific immunoglobulin E (IgE) that binds to certain cells in the airways and ‘activates’ them, leading to the release of chemical substances that cause allergic type inflammation. For this phenotype, treatment with high doses of inhaled corticosteroids may be effective or you may require medication that blocks IgE.

2. Late-onset severe eosinophilic asthma: characterized by an increase in the number of eosinophils (a type of white blood cell) in the respiratory tract. These cells have the ability to release chemical mediators that cause inflammation. Typically the disease has a late onset (after 18 years of age), occurs equally frequently in both sexes, and symptoms are not related to exposure to allergens (although hypersensitivity to allergens may be proven). Polyps in the nasal mucosa usually appear first, and after several years, asthma too, in the form of a severe disease right from the beginning. The clinical picture is dominated by severe disease exacerbations and daily symptoms, and a rapid loss of lung function occurs. The use of high doses of inhaled corticosteroids does not lead to disease control, and although chronic use of oral corticosteroids (OCS) can be effective, it is associated with a high risk of adverse effects. This form of severe asthma can sometimes be treated with medication that blocks the maturation, mobilization and survival of eosinophils in the airways, reducing their numbers, thus controlling asthma.

3. Aspirin exacerbated respiratory disease: is a subtype of late-onset, eosinophilic asthma in which, in addition to severe asthma, intolerance to non-steroidal anti-inflammatory medication (brufen, aspirin, novaletol, buscopan, etc.) and chronic rhinosinusitis with nasal polyposis is also present. This form of asthma is also associated with many symptoms and severe exacerbations, and eosinophilic inflammation is dominant. It is important to note that patients have symptoms even if they do not take non-steroidal anti-inflammatory medication, but taking them by accident results in sudden and very severe, possibly life-threatening, exacerbations.

The overlap of severe eosinophilic asthma with severe allergic asthma phenotypes is quite common in clinical practice. In both of these phenotypes there is eosinophilic inflammation of the airways, but it is more severe in non-allergic, late-onset eosinophilic asthma. An allergy can be involved in both phenotypes, but it is more distinct in allergic asthma. For this reason doctors can be uncertain as to which medicines will be the best for treating your severe asthma. If one group of medicines does not lead to the desired effect, another group can be tested. In order to ensure optimal treatment of your asthma, co-operation with your doctor and achieving good communication is key.

Severe asthma with dominance of Non-Type-2 inflammation

This category of severe asthma is still a great challenge as far as treatment is concerned, given that standard therapy is not effective, and biologics is currently unavailable. It can be divided into several sub-groups (phenotypes):

1. Severe neutrophilic asthma: usually occurs in adults, and the inflammation is dominated by neutrophils (the biggest number of white blood cells which play a defence role against infections). This type of asthma does not respond well to inhaled corticosteroids, and is usually associated with frequent bacterial or viral infections and changes to the smooth muscles of the airways. The treatment of this form of asthma is very difficult, sometimes small doses of certain antibiotics are used that can lead to a change in the immune response.

2. Severe asthma and obesity: in the clinical picture exacerbations are dominant. Standard treatments are usually unsuccessful so the body weight needs to be regulated.

3. Severe asthma and smoking: is a form of severe asthma that is associated with rapid deterioration of lung function, frequent exacerbations and bacterial infections. It is necessary to quit smoking in order to obtain any beneficial effect of the treatment.

Asist. dr sci. med. Sanja Hromiš
Institut za plućne bolesti Vojvodine, Sremska Kamenica