Page 18 - Winter 2024 Bulletin

Practitioners’ Corner
Asthma, phenotypes, endotypes, and comorbid
and coexisting conditions
Richard F. Lockey, MD rlockey@usf.edu
Asthma today is the most treat- able of all chronic diseases known to mankind. Although the symptoms, cough, wheezing, and dyspnea are common manifestations of the dis- ease, there are a variety of different asthma phenotypes, defined by their clinical characteristics, which have been better delineated over the past several decades. The most common phenotype is allergic asthma, but
there are a variety of other phenotypes including nonal- lergic, cough variant, late-onset, exercise-induced, occu- pational, aspirin-exacerbated respiratory disease, as well as asthma-COPD overlap syndrome (ACOS). Likewise, aller- gic bronchopulmonary mycosis is another phenotype.
Over the past decade or two, endotypes of asthma also have been identified. An endotype defines the mechanism and pathophysiology for the phenotype. These include eosinophilic, neutrophilic, mixed granulocytic, and pauci granulocytic, or in another way, polarized into two major asthma endotypes, TH2 high and TH2 low. These various delineations of types of asthma have led to a host of different treatment modalities, in particular, for severe asthma, which target various cytokines, depending on the endotype.
Of extreme importance is the fact that asthma is usually not an isolated disease but occurs with coexisting and co- morbid conditions that commonly accompany or exacerbate it. I first became interested in comorbid conditions of asth- ma approximately fifteen years ago when I was president of the World Allergy Organization. Based on this interest, I gave presentations and conferences throughout the world as well as publishing a book with my colleague, Dennis K. Led- ford, MD, entitled Asthma, Comorbidities, Coexisting Con- ditions and Differential Diagnoses. This book, published in 2014 by Oxford University Press brought more attention to these associated illnesses.
Even though the treatment of asthma has improved ex- ponentially over the past several decades, data based on emergency department visits and hospitalizations indicate that the diagnosis of asthma is still suboptimal and needs improvement. There are several reasons for this dilemma.
First, as stated above, asthma is not one disease, it is a com- plex heterogeneous syndrome consisting of different phe- notypes with defined endotypes. Second, it is influenced by known, unknown, avoidable, and unavoidable environ- mental factors with variable outcomes and severity. Third, patient education about how and when to take their medica- tions, both inhalational and others, is of optimal importance and often lacking. Fourth, asthma assessment is based on its symptoms, i.e., primarily cough, wheezing, and shortness of breath. However, too often, unrecognized and untreated comorbid and coexisting conditions add to its complexity. Comorbid conditions may play a role in the pathophysiology of asthma or cause exacerbations whereas coexisting condi- tions may not contribute to asthma but may result from it.
What are some of the main comorbid and coexisting con- ditions of asthma? First, asthma rarely occurs without a ma- jor upper airway problem, which may include allergic and nonallergic rhinitis as well as acute and chronic sinusitis, the latter with or without nasal polyps. It has been known for years that “how goes the nose, so goes the asthma.” Ev- idence-based medicine indicates that the upper and lower airways are “united.” The pathophysiologic changes in the lower airways also concurrently affect the upper airway, i.e., the mucosa of the laryngopharynx, nose, and sinuses, lead- ing to the term “united airways.”
Other comorbid conditions commonly seen include food allergy, a much more common problem today than in past years. Quite often, food allergy and asthma are associated with atopic eczema. It is not possible to treat a patient with asthma without also treating atopic eczema, and if present, food allergy.
There are a variety of different laryngeal and esophageal problems associated with asthma. They include vocal cord dysfunction, which sometimes can mimic asthma but often accompanies it and laryngopharyngeal and gastroesopha- geal reflux, both of which can play a primary or secondary role in causing or contributing to asthma symptoms. These include throat clearing, cough, and shortness of breath. Sev- eral other diseases associated with asthma often present with asthma signs and symptoms. These include hypersensitive pneumonitis, an inflammatory reaction of the lung second- ary to an abnormal immune response to antigens from birds,
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HCMA BULLETIN, Vol 70, No. 3 – Winter 2024