**5. Initiation and evolution**

mental endotoxin levels may have an outstanding role not only in adults but also from school

Conversely, if the asthmatic has a bacterial infection with respiratory location, it is most likely that obstructive symptoms will be intensified by the action of bacterial enterotoxins that act as superantigens, which promote the mechanisms by which the inflammation of the respiratory

**4. Pathogenesis of common symptoms in obstructive bronchopathies**

The mechanisms by which the symptoms of asthma occur in preschool children do not differ from those that cause the process at any age. The permeability of the bronchial lumen is maintained by a neuro-chemical mechanism, but airway calibre may be affected either by an imbalance in this mechanism or by the intervention of certain cells and their biochemical mediators involved in the inflammatory reaction, usually triggered in childhood by an allergic reaction or an unfavourable home environment. In the obstruction of the wider bronchi, the dominant mechanism is the constrictor one, of neuro-chemical cause, whereas in the peripheral bronchi (small airways), inflammation is the greatest cause, through cellular mediators that

BHR and inflammation are the pathogenetic basis of asthma. BHR is usually present already in the newborns of atopic families, although it is true that certain exogenous harmful agents can increase it. Similarly, the regular or intense exposure to these pollutants and also viral infections can cause broncholability in non-predisposed children. This increased bronchola‐ bility occurs as the result of inflammation that such elements, including allergens, produce in the bronchial mucous membrane. These facts are demonstrated in adults and children from school age, but in preschool children under five, the immediate influence of these exogenous factors is less certain. The injured bronchial epithelium is restored after the aggression that leads to crises of dyspnoea or wheezing, and the permanence of the injury can depend on the intensity of the aggression and the repetition of the same, leading to more or less severe and repeated symptoms. Therefore, there is doubt whether the inflammatory reaction is establish‐ ed from the onset of the first symptoms or whether that permanence occurs after the recurrence of the crisis or after the most serious crises, on which the therapeutic approach may depend. Various conventional methods are used to study bronchial inflammatory reactions, although in younger children, it is not always easy to conduct them. The most common are the following: Direct methods: (1) Cell study from sputum obtained by bronchoalveolar lavage (BAL),

Indirect, non-invasive methods: (1) Exhaled nitric oxide measurement. (2) Exhaled breath condensate: evaluation of several measurements of the inflammation. (3) Blood eosinophilia

The inflammatory reaction is a key event in the pathogenesis of asthma, as it is evident in adults and children from school age. It seems certain that inflammation is present even in the first

induced sputum, forced cough or aspiration. (2) Bronchial biopsy.

assessment and eosinophil cationic protein (ECP) in serum levels.

age, causing especially wheezy bronchitis or non-atopic asthma (6,10).

mucosa is established.

78 Asthma - From Childhood Asthma to ACOS Phenotypes

are also constrictors.

The precocity of the onset of episodes of respiratory distress may be related to the severity of the process and its evolution over time. Although in some children, the first crisis occurs in the first months of life, the process has a markedly evolutionary nature, not presenting the first crisis of dyspnoea but after a period of time, which varies from child to child.

#### **5.1. Asthma crisis: early onset**

For the suspected allergic asthma to be well-founded, it is necessary that the crisis is repeated for at least three times, as it is known that a large number of infants suffer an episode of dyspnoea, possibly of infectious cause, estimating that this happens in between 15 and 32% of children under 5 years, who cannot be labelled as asthmatics until the atopic cause is con‐ firmed, related to the progressive evolution of the process.

The first episodes of dyspnoea are usually caused by viral infections and occur most frequently in the cold months, and it is not uncommon that they are accompanied by light fever. Associ‐ ated symptoms are similar to asthma: rhinitis, dry cough, shortness of breath, wheezing, dyspnoea, intercostal retractions.

Depending on the intensity and the phase of the crisis, auscultation will show from wheezing to silent areas as well as fine or coarse crackles, indicative of bronchoalveolar involvement.

In any case, it is necessary to make sure there is a bronchiolitis, by RSV, of which prognosis and treatment can differ from that of a simple catarrhal process.

After the first year, it is likely that crises are not triggered by viral infections, but that other environmental factors are responsible, not ruling out weather conditions changes, even in atopic children.

The repetition of three episodes of dyspnoea should alert of the possibility that those are the first manifestations of asthma, which will continue in the following years. It is therefore necessary to assess in each case the various predisposing and boosting elements of atopy and asthma, such as the incidence of allergic disease in parents or close relatives, the coincidence in the child of other allergic processes or the environment in which the patient lives.

#### **5.2. Atopic processes precursors of asthma**

In chronological order, but not occurring in all cases, the first manifestation of atopy might be the sensitization to foods, mainly cow's milk when breastfeeding is absent, with symptoms in the first weeks of life. Eczema associated with sensitization to foods, from the third month, and rhinitis, as the first manifestation of respiratory allergy, that usually precedes asthma, both identities related with the persistence and increased intensity of the other two previous allergic processes.

The correlation between early sensitization to foods and later development of asthma is difficult to determine, but in these cases, given the repeated respiratory crisis by possible viral infection, the allergy study must be expanded.

#### *Atopic eczema*

Although atopic eczema may be the only manifestation of atopy in many children, there is no question about the relationship between eczema that start of in childhood and asthma, of which the first symptoms sometimes coincide with a cutaneous process, although in most cases, respiratory symptoms appear months or years later, even after skin lesions have disappeared or been attenuated, as it happens in many children before their third year.

To predict the risk of respiratory disease in children with eczema, an early allergologic study is advised. An elevated total serum IgE will be the early sign that will alert of the atopic nature of the process, but skin tests and assessment of serum IgE specific to foods and to the most common aeroallergens at home (mites, animal epithelium), which will alert about the risk of respiratory disease, which will start later.

Besides eczema, it is frequent that allergy to cow milk protein is revealed by digestive (vomiting, diarrhoea) or anaphylactic symptoms, which are also indicative of atopic predis‐ position and might be a precedent of asthma.

#### *Rhinitis, rhinoconjunctivitis, rhinosinusitis*

Not surprisingly, allergic sensitization is initially produced in the respiratory mucosa, as it is directly accessible to airborne allergens present in the air we breathe; and therefore, very often, respiratory pathology of allergic cause starts with symptoms of rhinitis. The frequency and persistence of nasal symptoms in early childhood are well-known fact, and their causes are diverse, from adenoiditis to allergic rhinitis.

Because of the proximity of the conjunctival mucosa, with similar characteristics to the respiratory one, it is not uncommon the concurrence with conjunctivitis (rhinoconjunctivitis). From the second or third year, it is neither uncommon the simultaneous conditioning of maxillary sinusitis, which may be limited to the inflammatory reaction of the mucosa, but that is often complicated by superinfection. Greater doubts arise in the relationship of rhinitis with otitis media present in some children, although it seems that nasal provocation with pollen can cause a dysfunction at the inner ear level.
