Asthma - what do we know about it?
Asthma is a disease characterized by chronic airway inflammation and bronchial hyperresponsiveness. Its typical symptoms are:
- dyspnea,
- tightness in the chest,
- coughing,
- attacks of wheezing.
These symptoms change over time and can be of varying severity – in some they are more, in others less intense. They are accompanied by ventilation problems, which we can detect through spirometry or pycnometry tests.
The development of asthma begins in the epithelium of the airways, and it should be noted that it has an impressive surface area – 100 square meters. It is there that the fight is initiated, which later moves deeper and causes the muscular contraction, bronchial thickening, and excessive production of secretions within the respiratory system.
Remission or cure?
As physicians, we would like to cure the asthma patient. For the moment, however, this seems impossible, although we have more and more arguments that say we are moving in the right direction. Depending on the type of asthma, we are left with “tailor-made” therapy that will achieve the best possible results.
The most severely ill patients are in a particularly difficult situation, because they are at the greatest risk of complications, and they also bear the greatest treatment costs. The international consensus of the Global Initiative for Asthma (GINA) [1] dictates that patients with severe asthma should be treated with biologic therapy. Thanks to it, we can count on remission, i.e. the cessation or significant reduction of symptoms, and, in the future, possibly also a complete cure.
But when exactly can we talk about remission? Unfortunately, at the moment there is no complete consensus on this among researchers [2,3]. Guidelines vary from country to country. According to the joint position of the Polish Society of Allergology and the Polish Society of Lung Diseases [3], we should be guided by the following division:
| Clinical remission during treatment | Clinical remission without treatment |
For ≥ 12 months (must occur together):
| criteria as beside persisting without anti-asthmatic treatment for ≥ 12 months |
| Complete remission during treatment | Complete remission without treatment |
Clinical remission + all of the following:
| criteria as beside persisting without anti-asthmatic treatment for ≥ 12 months |
GCS – glucocorticosteroids, FeNO – concentration of nitric oxide in exhaled air
Biological treatment of asthma
Even 20 years ago, we would have said that achieving the absence of bronchial hyperresponsiveness and its symptoms (coughing, wheezing, shortness of breath) in a person with asthma is impossible and remains a dream. Today, more and more studies confirm that such an effect can be achieved by causal treatment, namely biological therapy. This treatment intervenes in the inflammatory process within the respiratory system and changes the way the patient responds. With biological treatment, we are able to influence the mechanism of the disease. If we normalize epithelial function, we can tell the patient: “you no longer have asthma, you have been cured.” The question remains whether we will achieve sustained efficacy.
What do the guidelines say?
According to the GINA guidelines, biologic drugs should be given to patients who have failed to achieve disease control despite high doses of inhaled steroids used along with other disease-controlling drugs. Such a patient should undergo phenotyping (determining whether the inflammatory process in the lungs is T2- or non-T2-dependent). Typical symptoms of type 2 inflammation are elevated eosinocytes in the blood and elevated FENO levels in the exhaled air. If, in addition, the patient has had two exacerbations requiring oral steroids (i.e., encorton/polcortolone/medipred) within a year, then – according to the B44 drug program – they can receive free biological treatment at one of the 70 severe asthma clinics in Poland.
It is worth checking the correctness of aerosol therapy before qualifying a patient for treatment. Half of asthma patients use their inhalers incorrectly. Checking the correctness of aerosol therapy and a small adjustment in therapy can make a big difference. I encourage you to check how to correctly use inhaled medications in asthma on the asthma patients federation website or the Polish Society of Allergology website.
Latest scientific reports on biological treatment of asthma
- According to the ANDHI study, the use of benralizumab in 83% of patients achieved ≥ 2 remission criteria. So, 83 people out of 100 were able to wean off the oral steroid, moreover, 1 out of 4 no longer had any symptoms, although, after all, they all started treatment with severe asthma [2,3,5].
- The SHAMAL study shows that with benralizumab therapy we can not only reduce asthma symptoms, wean off oral steroids, and improve spirometry, but also, as GINA encourages us to do, lower the dose of inhaled steroids (to moderate or low). After 48 weeks of benralizumab therapy, this was possible in 92% of patients with severe asthma. Despite the reduction in ICS, asthma control was maintained [6,7].
In addition, it should be noted that such treatment also reduces the number of hospital stays.
As seen with another biologic drug, tezepelumab, we can also affect one of the more bothersome symptoms of asthma – excess mucous secretions that suppurate the bronchi. The occurrence of mucous suppositories is associated with bronchial lumen narrowing and ongoing eosinophilic inflammation [9,10,11,12,13]. The drug acts at the level of the respiratory epithelium – reducing asthma symptoms, reducing the number of exacerbations and significantly improving lung ventilation efficiency. It has been proven that this particular drug significantly reduces bronchial hyperreactivity – a typical feature of asthma. Without hyperreactivity, there is no asthma. So we may be close to a real breakthrough.
We can also use tezepelumab in patients with non-T2-dependent inflammation in the airways.
Similarly, mepolizumab, a drug that reduces the number of acidophilic cells (eosinocytes) infiltrating the mucosa of patients with asthma, has a similar anti-eosinophilic effect. The use of mepolizumab significantly reduces the frequency of exacerbations of the disease, allows the majority to discontinue oral steroid therapy, and improves lung function. Moreover, it has registrations in all eosinophilic diseases: asthma, sinusitis with polyps, as well as EGPA (eosinophilic granulomatosis with vasculitis), HES (hypereosinophilic syndrome). Fortunately, the latter two diseases are very rare [17].
Prevention is better than cure
So there is no doubt that biological therapies are a very promising treatment option. But in practice, they are used only in severe forms of the disease. So maybe it’s worth going back to the beginning and thinking about whether something can be done so that the patient doesn’t develop asthma at all. The way to do this is to quickly incorporate causal treatment (immunotherapy), which can make it so that all that allergen-induced respiratory distress doesn’t occur at all.
Allergologists should follow the maxim that prevention is better than cure and remember the role of allergen prophylaxis. If a patient’s asthma was triggered by a mite allergy, then by using anti-mite immunotherapy – so-called desensitization – we can remove the root cause of the disease and thus reduce the amount of medication needed to ensure the patient’s well-being.
Stop Atopic Disease
Allergic asthma, if contact with an allergen occurs continuously, is very difficult to treat. It is much easier to affect the cause through early intervention. Sometimes (if the patient has severe atopic dermatitis) this can be immediate biological treatment. It is worth recalling that dupilumab in AD is used as early as 6 months of age.
Dupilumab normalizes epidermal barrier function, preventing the development or progression of concurrent atopic diseases. This is extremely important, since a dysfunctional skin barrier allows transdermal penetration of allergens and the development of further sensitization [14]. Moreover, the drug has a comprehensive effect on the entire T2-dependent inflammation. It alleviates the symptoms of AD, removes the symptoms of chronic sinusitis and reduces the symptoms of bronchial asthma. Its use in childhood prevents the development of asthma in adolescents and young adults. In already diagnosed severe asthma, dupilumab reduces the number of exacerbations and allows oral steroids to be discontinued, reducing the health costs of the disease.
Keep in mind that the entire history of atopic disease, or allergic march, begins in infancy. Often, AD in an infant later leads to symptoms from the upper and lower respiratory tracts, and often the gastrointestinal tract. The earlier we start treating allergies, the fewer sufferers will have asthma symptoms.
Dr hab. Piotr Dąbrowiecki
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translation: Julia Majsiak
