Asthma is a disease of the airways characterized by airway inflammation that is partially reversible. Medical treatment has been designed with this definition in mind. It has been evident that not all asthmatics respond to treatment the same way. In particular, people diagnosed with severe asthma have unique and difficult treatment challenges because their subtype of asthma is resistant to traditional therapy.
The Severe Asthma Research Program (SARP) is a survey and follow up of individuals with the characteristics of severe asthma conducted by the National Institute of Health (NIH) and National Heart, Lung and Blood Institute. The purpose of the study is to gain insight into the clinical, cellular, and biological characteristics of this severe asthma group.
Some of these findings resulted in further classifying individuals with severe asthma into separate subgroups called phenotypes. These subgroups have common characteristics such as age of onset, allergy base, responsiveness to steroids, and are associated with obesity and eosinophilic inflammation.
While much has been said about severe asthma being related to possible permanent narrowing of the airways due to remodeling, nothing has been said about changes in the structure and size of the lungs themselves.
A March 2018 study looked at a new manifestation in people with severe asthma, which has typically been more characteristically associated with COPD and emphysema.
Emphysema is a condition that results in changes in the size of the lungs. The lungs retain larger levels of air but have a decrease in the ability to exhale or expel that air because of loss of lung elasticity (loss of recoil).
The study published in the journal Chest followed severe asthmatics who were non-smokers. The researchers selected the group that fit into the Type 2 phenotype. This group had levels of blood eosinophils, the presence of an allergy component measured by high levels of IgE antibody, and abnormal counts of exhaled nitric oxide. These are markers of inflammation. The study goal was to investigate consequences of persistent silent inflammation.
Specifically, the goal of this research was to determine the loss of elastic recoil and to note early emphysema changes in these individuals. This was done using high resolution CT scanning - a CT scan of the chest that takes measures every one mm. This method then allows for is a quantification of the extent of hyperinflation in the lungs.
The researchers also measured the changes in the airflows in the lungs of these subjects. Airflow can be measured at various points and in this case they measured the airflows at mid-flow. The airflow at this level reflects “effort dependent,” meaning a person uses effort to breathe.
In healthy people, inspiration (taking in air) has to first overcome the resistance in the upper point of the airways, as air then begins to enter the smaller airways. The large number of small airways at this point, allows airflow to happen without use of respiratory muscles. This is called the “effort independent airflow.” No real effort is required.
In people diagnosed with emphysema, this portion of flow encounters high resistance because of the excess air remaining in the lungs because of incomplete expiration (hyper-inflated lungs). The person with emphysema has to use effort even at this early stage of breathing.
In the severe asthma group that the study focused on, mid flow was also abnormal, indicating that these individuals have changes consistent with emphysema. Specifically, it indicates that these individuals with asthma were losing the elastic recoil of the lungs. As mentioned earlier, this physical feature would be found in people with emphysema.
In fact, this finding has been a classical feature of COPD. Asthma has been known to have many features of permanent damage to the lungs that are not responsive to therapy. However, emphysema has not been described before as a feature of severe asthma. And in this case, there was no contributing factor of smoking to increase the risk in this populace of developing emphysema.
What are the implications of this finding? Given the different characteristics of COPD and asthma, new observations are highlighted:
There are (clearly) different inflammatory triggers for both asthma and emphysema.
There are different genetic presentations of individuals which guide the tendency of the airways and lungs to react differently and develop different consequences.
- Different diagnostic testing is necessary to determine different types of obstructive lung disease.
All these observations, most importantly, have implications with regards to treatment in the severe asthma population. We can also no longer assume that smoking history alone will determine whether one has COPD or asthma.
Whereas asthma has been traditionally thought of as being a disease of the airways, with inflammation and bronchospasm at the root of the pathology, studies have found that the cause of emphysema in people with asthma rests in abnormality in the alveolar attachments. This is a new finding that may explain the presence of and identification of emphysema in someone with asthma who never smoked.
There have been anecdotal theories like the Dutch Hypothesis offered as far back as the 1960s to suggest that that bronchial hyper-responsiveness in young individuals were determinants of advanced COPD in adults, but because this and other theories were based on anecdotal findings and not exclusively hard science, they’ve been debated for years. Many experts have suggested that asthma and COPD are distinct conditions. This latest study now gives credence to the possible presence of asthma and COPD in individuals, and specifically when smoking was not a risk factor.
The takeaway message is that if you have asthma that seems to be resistant to standard treatments, severe asthma should be a strong diagnostic consideration and depending on symptoms and complaints, doctors should also consider the possibility that emphysema can be a co-morbid condition even in the absence of a smoking history.
See more helpful articles:
Biologic Medicines for Asthma: Understanding Clinical Trials
Thermoplasty: A New Treatment for Resistant Asthma
Barrel Chest: An Explainer