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Thus, the relationships between the three classic components of asthma are more complex than previously thought, and this is highly relevant to considerations of pathophysiology.
The conventional view of at least school age and adult asthma is that the root cause is airway inflammation, which leads to airway hyper-responsiveness, and, secondary to repeated episodes of inflammation, airway remodeling.
However, a critical review of the evidence shows that this view is untenable.
There is only a weak correlation at baseline between eosinophilic inflammation and bronchial hyper-responsiveness (6, 7).
The anti-Ig E monoclonal omalizumab reduces airway eosinophilia, but has no effect on bronchial hyper-responsiveness (8), whereas the anti-TNF monoclonal etanercept reduces hyper-responsiveness but has no effect on airway inflammation (9).
Additionally, the pathophysiology of risk domains must be considered: these are risk of an asthma attack, risk of poor airway growth, and in pre-school children, risk of progression to eosinophilic school age asthma.
Phenotyping the airway will allow more precise diagnosis and targeted treatment, but it is important to move to endotypes, especially in the era of increasing numbers of biologicals.Furthermore, there is no relationship between the extent of airway remodeling, specifically reticular basement membrane thickness, and the degree or duration of any inflammatory parameter (10).Indeed, there is evidence that remodeling may be protective under some circumstances, discussed in more detail below.The next step is to deconstruct the airway into components of fixed and variable airflow obstruction, inflammation, infection and altered cough reflex, setting the airway disease in the context of extra-pulmonary co-morbidities and social and environmental factors.The emphasis is always on delineating treatable traits, including variable airflow obstruction caused by airway smooth muscle constriction (treated with short- and long-acting β-2 agonists), eosinophilic airway inflammation (treated with inhaled corticosteroids) and chronic bacterial infection (treated with antibiotics with benefit if it is driving the disease).Sophisticated –omics approaches will be reviewed in this manuscript, but currently they are not being used in clinical practice.However, even while they are being evaluated, management of the asthmas can and should be improved by considering the pathophysiologies of the different airway diseases lumped under that umbrella term, using simple, non-invasive tests which are readily available, and treating accordingly.The result has been the specific, molecular therapies (2–4), none of which would have come to the bedside if they had been tested on every child with a chronic wet cough.It is also important, but largely outside the scope of this chapter, to set airway disease in the context of extra-pulmonary co-morbidities such as obesity, and environmental and lifestyle factors, such as adverse environmental exposures and adherence (5).These are: • Narrowing to cause fixed obstruction • Narrowing to cause variable obstruction which changes spontaneously over time, and with treatment • Inflammation with various cell types predominant; inflammation may be harmful or beneficial • The tube may become infected with combinations of bacterial, viral and fungal pathogens • There may be increased “twitchiness” of the tube—this is different from variable obstruction.An increased reflex expulsive effort (cough) may not be accompanied by transient airflow obstruction • The tube contents may be abnormal: including being too wet, too many solids, or too dry.