**6. Clinical and allergologic diagnosis**

The diagnosis of asthma in the first years of life is based on a thorough questioning (anamnesis) and in the allergologic study. Given the difficulties and controversies surrounding the concept of the disease at a such early age, the issue is to obtain data that, with the smallest possible doubt, may allow on one hand to establish the syndromic diagnosis, that is, the existence of intermittent episodes of bronchial obstruction and, on the other, allergic causality, in most cases, or the responsibility of other exogenous factors able to increase bronchial reactivity, which usually occurs at later ages. When the allergologic study is negative, the questioning may provided valid information to guide diagnosis to some other of the process in which coughing or signs of bronchial obstruction often dominate the case history, having to complete the study in accordance with the suspected diagnosis.

Physical examination is essential, since even if the child is asymptomatic while being exam‐ ined, important data, such as a chest deformity, the presence of paradoxical breathing with depressed abdomen on inspiration, or the pathologic auscultation when the child breathes deeply, among other information, can be obtained. Moreover, functional exploration will also provide data that can be decisive for the definitive diagnosis.

#### **6.1. Anamnesis**

asthma, such as the incidence of allergic disease in parents or close relatives, the coincidence

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

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

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

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

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‐

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

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

or been attenuated, as it happens in many children before their third year.

in the child of other allergic processes or the environment in which the patient lives.

**5.2. Atopic processes precursors of asthma**

80 Asthma - From Childhood Asthma to ACOS Phenotypes

infection, the allergy study must be expanded.

respiratory disease, which will start later.

position and might be a precedent of asthma.

diverse, from adenoiditis to allergic rhinitis.

*Rhinitis, rhinoconjunctivitis, rhinosinusitis*

processes.

*Atopic eczema*

A good interrogation often provides critical data to guide the diagnosis. It should include information about family precedents and medical history, diseases of probable allergic cause cited above, symptomatology, chronology of symptoms, medication use and its effectiveness.

#### **6.2. Other medical history**

Primary immunodeficiencies also occur in repeated bronchopaties, by viral or bacterial infections, with symptoms that may remind those of asthma; hence, the need for information on whether there have been relatives with any of these diseases (Wiskott–Aldrich, Hypo or agammaglobulinaemia, Di George, etc.), processes in which predisposition is transmitted by recessive inheritance.

#### **6.3. Symptomatology: chronology**

It is not enough to know that the child has episodes of cough or dyspnoea, but it must be also known if the cough is dry or soft, if breathing difficulty improves or worsens after a coughing spell, if there is expectoration, or if it is predominant at night, among other features. It is also necessary to know the intensity of respiratory distress, if it is accompanied with nasal flaring, or if it disrupts sleep. The existence of fever is also a point of great interest because an infectious trigger can be assumed.

The chronology of the succession of symptoms in each episode is another fact of interest, as it is whether dyspnoea appeared abruptly or was preceded by nasal or pharyngeal symptoms, as well as at what time it began, for example, if it was at night or after eating some food. The biggest interest is in the chronology of the process, taking very much into account the age at which symptoms started and whether they were intense from the beginning (mucoviscidosis could be suspected of).

#### **6.4. Medication: use and effectiveness**

Usually, when a child presents some of the symptoms that characterize bronchial obstruction, some medication is usually given, and their effectiveness must be critically evaluated, in order to better guide the diagnosis. It is not always possible to reduce or eliminate breathing difficulty with a bronchodilator, when mucous secretion is predominant, or preventing relapse with an inhaled corticoid, when there is no inflammation because the airway obstruction is of another nature.

#### **6.5. Allergologic study**

#### *Skin tests*

They may already be positive even in the second month of life, to cow's milk protein (casein, β-lactoglobulin). At 4 months, it is possible to show sensitization to other foods, especially egg proteins, increasing the percentage in the coming months, as new foods are introduced. Sensitization to pneumoallergens comes later. It is estimated that approximately 40% of atopic children under 3 years are sensitized to dust mites, reaching 70% in those over 4 years. Figures for animal epithelia range from 3 to 5% in the younger, being 6–8% at around 4–5 years of age. Sensitization to pollens also depends on the place of residence, in relation to the time and intensity of exposure.

The *prick test* is the least traumatic and totally reliable and reproducible technique that has replaced intradermoreaction. It is virtually painless, very well accepted by young children and easily performed with the same technique at any age.

Usually, the study is limited to dust mites, the most common being *Dermatophagoides ptero‐ nyssinus* and *Dermatophagoides farinae*, but others can be added, such as *B. tropicalis, Acaro siro* or others that are common in the geographical area of residence: animal epithelia, cat and dog (the most frequent, even if they are not present at home) or other animals with which they may have contact. Fungi can be found anywhere at home. The most important, that allow conduct‐ ing immunotherapy, are *Alternaria tenuis* and *alternata*, and *Cladoporium* ssp. At homes with high humidity, other fungi must be tested, such as *Aspergillus, Penicillium, Fusarium, Mucor,* etc. Earlier than at 3–4 years of age, sensitization to pollens is unlikely, although there is no objection to include in the list of allergens a mixture of pollen from wild grasses (*Poa pratensis, Festuca, Dactylis glomerata, Lolium perenne, Phleum pratense*) that are most often sensitizing. Other pollens depend on the geographic area in which they reside.

#### *Total serum and specific IgE*

The chronology of the succession of symptoms in each episode is another fact of interest, as it is whether dyspnoea appeared abruptly or was preceded by nasal or pharyngeal symptoms, as well as at what time it began, for example, if it was at night or after eating some food. The biggest interest is in the chronology of the process, taking very much into account the age at which symptoms started and whether they were intense from the beginning (mucoviscidosis

Usually, when a child presents some of the symptoms that characterize bronchial obstruction, some medication is usually given, and their effectiveness must be critically evaluated, in order to better guide the diagnosis. It is not always possible to reduce or eliminate breathing difficulty with a bronchodilator, when mucous secretion is predominant, or preventing relapse with an inhaled corticoid, when there is no inflammation because the airway obstruction is of another

They may already be positive even in the second month of life, to cow's milk protein (casein, β-lactoglobulin). At 4 months, it is possible to show sensitization to other foods, especially egg proteins, increasing the percentage in the coming months, as new foods are introduced. Sensitization to pneumoallergens comes later. It is estimated that approximately 40% of atopic children under 3 years are sensitized to dust mites, reaching 70% in those over 4 years. Figures for animal epithelia range from 3 to 5% in the younger, being 6–8% at around 4–5 years of age. Sensitization to pollens also depends on the place of residence, in relation to the time and

The *prick test* is the least traumatic and totally reliable and reproducible technique that has replaced intradermoreaction. It is virtually painless, very well accepted by young children and

Usually, the study is limited to dust mites, the most common being *Dermatophagoides ptero‐ nyssinus* and *Dermatophagoides farinae*, but others can be added, such as *B. tropicalis, Acaro siro* or others that are common in the geographical area of residence: animal epithelia, cat and dog (the most frequent, even if they are not present at home) or other animals with which they may have contact. Fungi can be found anywhere at home. The most important, that allow conduct‐ ing immunotherapy, are *Alternaria tenuis* and *alternata*, and *Cladoporium* ssp. At homes with high humidity, other fungi must be tested, such as *Aspergillus, Penicillium, Fusarium, Mucor,* etc. Earlier than at 3–4 years of age, sensitization to pollens is unlikely, although there is no objection to include in the list of allergens a mixture of pollen from wild grasses (*Poa pratensis, Festuca, Dactylis glomerata, Lolium perenne, Phleum pratense*) that are most often sensitizing.

could be suspected of).

**6.5. Allergologic study**

intensity of exposure.

easily performed with the same technique at any age.

Other pollens depend on the geographic area in which they reside.

nature.

*Skin tests*

**6.4. Medication: use and effectiveness**

82 Asthma - From Childhood Asthma to ACOS Phenotypes

From birth, the serum non-specific IgE level increases to reach figures close to those of the adult into adolescence (**Table 2**). IgE has some physiological functions, such as defence against helminth parasites, although it is supposed to participate in other defence mechanisms. In the atopic individual, the regulator mechanism of IgE production is genetically altered by the prevalence of the activity of Th2 lymphocytes already mentioned. Therefore, it is common in these patients to find an elevated serum IgE level, not having yet been specifically produced against any allergen. Hence, the finding of an elevated total serum IgE may be linked to symptoms suggestive of allergic disease, and in consequence, this finding has considerable guidance significance. However, in any case, it must be taken into account that the possibility of elevated total serum IgE, especially if the figure is very high, might be related to other processes such as parasites or certain immunodeficiencies (**Table 3**).

The assessment of total and specific to allergens IgE is based on radioimmunoassay, fluoro‐ metric or enzyme techniques. As a first step, in a suspected allergic disease, a method that includes a mixture of allergens that are suspected to be frequent in childhood (food and airborne allergens: Phadiatop® infant, Immuno-CAP, 3gAllergy) can be used, the positivity of which may indicate specific sensitization to any of the antigens included. Subsequently, the allergen that led to the positive test must be identified in order to establish the preventive and specific treatment as appropriate.

Comparing the diagnostic value of skin tests and the specific IgE, it can be said that both are equivalent; however, it is always advisable to check the diagnosis with both tests. To comple‐ ment the immunoallergologic study, it is required to assess other serum immunoglobulins, IgG, IgM and IgA, as it is not uncommon that the deficit of some of them may favour respiratory infections. It is not unusual that this happens when there is selective deficiency of IgA, a common immunodeficiency (1/700 in the general population and 1/200 people with allergies) that sometimes goes unnoticed by a low clinical expression in most cases.

#### *Eosinophilia: cationic protein*

In peripheral blood, increased eosinophils above 500 cells/mm3 may indicate allergic reaction in any organ system (lung, skin, digestive tract) where the process is in an acute phase or immediate to clinical reaction. The presence of eosinophils in the bronchial exudate or tissue obtained by biopsy reveals the characteristic inflammation of an allergic reaction. When not in these cases, eosinophilia may be normal, and very high levels are usually due to many processes, parasitosis most of the time.

More valuable is the elevation of serum level of the enzymes from eosinophils, mainly ECP, easy to determine. It is necessary to be cautious when assessing the increased serum ECP as a marker of a certain bronchial inflammation, given the variability of the figures that can be found. According to Koller et al*.* [12], it could be a good marker even after the first episode of dyspnoea, finding a higher ECP in infants which a year later were diagnosed with asthma than in those who did not developed the disease, estimating that figures higher than 20 μg/l could have a strong prognostic value. However, Pohunek et al. [23] found no differences in ECP levels in children under 3, between both diagnoses when children were asymptomatic, as opposite to when they were suffering a crisis. From his work, it can be deducted the inter‐ est to assess the enzyme during a bronchobstructive crisis, in yet not diagnosed children, es‐ pecially during the first episode, for the possibility of establishing prophylactic measures to prevent or delay the establishment of asthma.


**Table 2.** Normal serum IgE levels (Kjellman and Johanson, 1976).


**Table 3.** Non-allergic process more frequents in small children that occur with high IgE.

Since allergic rhinitis often precedes the onset of bronchial symptoms, eosinophil count and ECP in nasal mucus can be a good indicator of allergic predisposition and the possible progression of the disease to the lower airways. Presence of allergy will be suspected if the percentage of eosinophils of the total cells of the smear exceeds 10%. In the same sample, ECP and even total and specific IgE can be assessed, in which variation after immunotherapy can be a good indicator of the effectiveness of the treatment [15].
