Many people are referred to our practice with longstanding symptoms of cough. While our management of such patients is tailored to the individual, and depends very much on the presenting history (characteristics of the cough, sputum production, smoking history, dangerous exposures etc) there are some investigations which we perform very frequently. Of course, spirometry – that first and most basic of investigations – is performed almost universally. It helps pick up people with uncontrolled asthma or chronic obstructive pulmonary disease almost before they come in the door.
Many asthmatic patients will, however, have entirely normal spirometry. In such patients, the diagnosis of asthma will often be made with bronchoprovocation studies.
We perform mannitol bronchoprovocation studies frequently in our lab. They are an important part of the evaluation of many patients with chronic cough. For this reason I have been reading with interest the results of a very small study published in Respirology journal in April; a study which looks at the differences between asthma and eosinophilic bronchitis with regards to indirect bronchoprovocation challenges, such as mannitol bronchoprovocation.
First, a brief word about these two diagnoses. I explain to all of our patients with newly diagnosed asthma that there are two important aspects to the pathology of asthma in the airways which need to be understood, and which make sense of why we use the medications we do. Those two are:
- airway inflammation
- airway hyperresponsiveness.
The former is usually mediated by allergic processes in kids, but is more of a mixed bag in adults. ‘Mast cells’ ( a type of white blood cell particularly involved in some allergic reactions) infiltrate the airway lining and muscle. Inhaled steroids help suppress this process. The latter process involves contraction of airway muscles, often experienced as breathlessness and chest tightness. Medications such as salbutamol, an asthma ‘reliever’ help control this process (as do formoterol and salmeterol).
This Journal paper reminds us that eosinophilic bronchitis, estimated to be the cause of cough in up to 15% of chronic cough seen in chest clinics, sees a disconnect between the two processes. That is, mast cell-mediated inflammation occurs in the airways (with lots of ‘eosinophils’ in an induced sputum or bronchoscopy sample) without airway hyperresponsiveness. This is not a new idea. The definition of EB is essentially that there is eosinophilic airway inflammation without abnormal airflow on spirometry and without a drop in lung function on bronchprovocation testing with methacholine. However, airway inflammation in asthma has been demonstrated to be better associated with hyperresponsiveness to mannitol than to methacholine. Likewise, some asthmatics will react to indirect challenges and not to direct challenges. This study was arranged to further test the hypothesis that EB really does exist, I suppose, and to really prove that patients with EB do not have airway hyperresponsiveness to indirect challenges.
This hypothesis was tested in a small number of patients. Patients with diagnoses of EB (all of whom had had previous mannitol bronchoprovocation) and patients with a diagnosis of asthma were compared with each other and with healthy controls. An induced sputum sample was obtained on the day that tests were performed to help confirm the diagnoses. Bronchoprovocation studies were then performed with either AMP or mannitol (both ‘indirect’ challenges that lead to airway hyperresponsiveness in asthma via secondary pathways ) or both.
Now the study was small. There were only 11 healthy and 14 asthmatic patients, with 8 patients suffering from eosinophilic bronchitis. Asthmatic and EB patients had similar levels of eosinophils in their sputum, where healthy controls had none. Asthmatic patients generally reacted to the indirect challenge (7 of 10 asthmatic patients given mannitol had positive responses). None of the healthy controls or EB patients reacted to the mannitol (or to the AMP).
This paper is a good reminder of the diagnosis of eosinophilic bronchitis. I like the idea they put forward that this is a process where the inflammation occurs only in the airway mucosal lining and not in the smooth muscle. I’d like to know for certain, however, that simple treatments like inhaled steroids help. In my experience that’s not necessarily the case, although the disease is supposed to be very responsive to inhaled steroids. The problem at that point is that in asthma we have useful tools such as spirometry and bronchoprovocation studies for objectively monitoring our treatment regimes. In EB, when those tests are normal to begin with, it’s difficult to know how to objectively evaluate treatment effect when symptoms don’t settle.
Andrew
No comments:
Post a Comment