Modificări fiziopatogenice ale tractului respirator în tranziția de la copil la adult

Introduction

The respiratory tract begins to form from the first weeks of intrauterine life and continues to develop throughout childhood. The process is complex, with particular implications for respiratory and immunological pathology, especially at pediatric age. There are important aspects which are a direct consequence of the correct development of the respiratory tract. Among these, efficient breathing ensures adequate gas exchange at the alveolar-capillary membrane. This provides oxygen, which is absolutely necessary for cellular respiration and removes the resulting carbon dioxide. A well-developed respiratory tract involves and helps protect the body against respiratory infections through effective adaptive immune responses. A good respiratory function is essential for the normal growth and development of children.

As the child grows, the respiratory system continues to develop and adapt to the body’s needs. Lung function and respiratory capacity gradually improve, with morphofunctional particularities at different ages. In childhood, organs and systems undergo a continuous process of maturation and development, with subsequent changes in structure, physiology, localization and neurological control. Somatic and functional development is particularly evident in the airways, especially in the first two years of life, so that by the age of 6-8 years old, the pediatric respiratory system becomes very similar to that of the adult.

Respiratory pathology has a high prevalence in pediatrics, both due to innate, subsequently adaptive immunity and age-dependent peculiarities of pathogenic response. Understanding the developmental particularities of the various components of the respiratory system in the context of current pathogenic challenges could provide a more effective personalized approach by the pediatric practitioner. 

In this article, we will present the anatomical transformations, physiology and pathogenic features of the respiratory tract segments from the young child to adulthood. 

Nasal fossa

The nostrils grow rapidly in size in the first five years of life, when the volume between the nostrils and the larynx reaches 40.3% of that of an adult. The nasal turbinates show the most noticeable growth during infancy. The nostrils are circular in the newborn, oval in childhood, and elongated in adulthood. Small nostrils or incomplete development of the nostrils can cause breathing problems, as the nose contributes up to 50% of the total airway resistance in young children. Mild nasal obstruction due to mucus congestion or mucus production increases breathing effort in infants and can cause respiratory distress. This phenomenon is accentuated in the supine position, when respiratory biomechanics are also altered, especially in infants and young children. Thus, minimal congestion of the nasal mucosa or mucus accumulation, even in small amounts, can cause respiratory distress in infancy⁽¹⁾. 

Paranasal sinuses

They are air-filled cavities located in the bones of the skull and face around the nose. In children, these sinuses develop and mature as they grow. The maxillary sinuses begin to form in the prenatal period and continue to develop until adolescence. The ethmoid sinuses are present at birth and continue to grow until about the age of 12 years old. The frontal sinuses begin to form at age 2 and continue to develop until adolescence. The sphenoid sinuses begin to form at 3-5 years of age and continue to develop until adolescence. Thus, the ethmoid and maxillary sinuses are already present at birth, while the frontal and sphenoid sinuses develop later, being radiologically demonstrated at the age of 5-6 years old and in adolescence, respectively. Because the sinus mucosa comes in continuity with the nasal mucosa, the risk of transmission of infection to the sinuses is high. Inflammation of the sinuses is accompanied by pain, tightness, inadequate aeration and accumulation of mucus or purulent collections.

Mouth and pharynx

In young children, the tongue is large and completely occupies the oral cavity. The base of the tongue is closely connected to the epiglottis, which extends towards the velum, whereas in adults there is a wider space between the two structures. Infants have a shorter neck and lar­ger head in relation to body size and a prominent occiput; as a result, when supine, the alignment of the oral, laryngeal and tracheal axes is hampered by excessive neck flexion, with a high risk of upper airway obstruction. Thus, a difficult visualization of the glottis is achieved during laryngoscopy. Placing a folded towel roll under the shoulders allows the neutral positioning of the neck, improving airway alignment⁽²⁾. 

The pediatric pharynx is shorter and has a smaller cross-sectional diameter than the adult pharynx. The nasopharynx and oropharynx house Waldeyer’s ring, which is composed of lymphoid structures and the lingual, tubal and palatine tonsils; these lymphoid structures are frequently enlarged in children because they grow rapidly until the age of 5-7 years old, and then undergo physiologic atrophy, especially in the absence of sustained antigenic stimulation, in the toddler period (innate immune response). This increased lymphoid tissue mass may contribute to airway obstruction in children⁽³⁾.

The Eustachian tubes open on the lateral wall of the nasopharynx. These structures, which connect the middle ear to the pharynx, are shorter, flaccid and more horizontal at birth, making it easier for mucus to stagnate, especially in a prolonged supine position. Eustachian tubes grow rapidly during the first year of life.

Larynx

During childhood, the larynx is located in a more cephalic and anterior position than in adulthood. In newborns and children up to 2 years of age, the lower limit of the cricoid cartilage is at the level of the fourth cervical vertebra. By the age of 6 years old, the cricoid cartilage goes up to the level of the fifth cervical vertebra, and by adulthood it reaches the level of the sixth cervical vertebra.

The visualization of the vocal cords by direct laryngo­scopy is difficult in infants and young children. The laryngoscopic view is hampered by the epiglottis, which appears larger, longer and more omega-shaped (Ω) than in older children. In addition, the epiglottis is more horizontalized than in adults (45° angle compared to 20° to the anterior pharyngeal wall). Because of the higher position of the larynx, the tip of the epiglottis almost reaches the soft palate: this anatomical conformation allows the infant to breathe and suck simultaneously without aspirating due to the intermittent pressure of the tongue on the soft palate (the so-called “veloglossal sphincter”).

These anatomical peculiarities, together with immature coordination between respiratory effort and oropharyngeal motor and sensory innervation, explain why infants have long been considered “preferential nasal breathers” until 2-6 months of age. During this age range, infants improve their ability to mouth-breathe outside of crying by detaching the soft palate from the tongue in a progressively enlarged oral cavity⁽⁴⁾.

In adults, the vocal cords are angled at almost 90° to the trachea, whereas in children the angle is more oblique, as their vocal cords extend posteriorly and superiorly, making laryngoscopic vision even more difficult. In addition, they are not linear but concave, because the vocal process of the arytenoid cartilage is inclined inferiorly and medially. 

Articulate speech becomes possible when the larynx begins to descend (around the second year of life), so the tongue has more room to move and the vocal cords are less inclined. In terms of consistency, the pediatric larynx, with the exception of the hyoid bone, is composed of unossified cartilaginous structures; therefore, the entire structure is softer and more flexible than in adults, which increases the risk of airway obstruction. Complete calcification of the components of the larynx and trachea occurs in adolescence.

Trachea

The trachea is shorter, narrower and posteriorly inclined in children. Due to the higher position of the pediatric larynx, the cervical segment of the trachea appears to be composed of more tracheal rings in children than in adults, with ten countable rings above the sternal manubrium in neonates, eight in adolescents, and six or fewer in adults. In addition, in the infant, the size of the trachea is approximately 50%, 36% and 15% of the length, diameter, and cross-sectional area of the adult trachea, respectively⁽⁵⁾.

Bronchi and bronchioles

In children, the bronchi are narrower and shorter than in adults. The bronchi and bronchioles continue to develop and grow into adulthood. Mucus production and the presence of cilia help protect the lungs against foreign particles, bacteria and viruses.

The “preacinar” or conductive airways are considered complete at birth, being described as a miniature version of adult structures. They only enlarge and elongate during growth, doubling or tripling in size by adulthood⁽⁶⁾.

Lung

While the development of the conductive airways is complete before birth, the lungs undergo a prolonged period of postnatal development and maturation. Lung development is characterized by four phases (five if the embryonic period is taken into account, during which the respiratory tract develops from the foregut at about 3-5 weeks of gestation), as follows.

• In the “pseudoglandular phase”, which occurs at 5-16 weeks of gestation, the preacinar branched airways and primitive capillary plexus begin to develop and the mesenchyme is abundant. By the end of this stage, the bronchial tree is fully formed.
• The “canalicular phase” occurs between 17 and 27 weeks of gestation, being characterized by the development of primitive alveolar acini. In this phase, types I and II pneumocytes begin to differentiate, so that they can be recognized after 24 weeks of gestation. It is a stage of increasing capillarization, which also becomes closer to the surface epithelium of the airways, as well as a decrease in the amount of connective tissue, which indicates the beginning of the development of the alveolar-capillary barrier.
• The “saccular phase” begins at 28-36 weeks of gestation and continues until birth; type II pneumocytes begin to produce surfactant, the saccules develop, and the respiratory units differentiate. This phase is crucial: babies born before 36 weeks may have respiratory distress requiring exogenous surfactant.
• Although true alveoli begin to appear around 28 weeks of gestation, the last phase – the “alveolar phase” – conventionally starts at 37 weeks, as alveolization occurs mainly after birth. In fact, at birth, newborns have between 17 and 71 million alveoli, while adults have between 200 and 600 million, so 85% of alveoli are added postnatally.

Lung volume doubles by 6 months of age, triples by 1 year, and increases about 13-fold between 1 month and 7 years old. Airway growth is slower than parenchymal growth, especially in the first year of life. The process of alveolization is not yet completely understood. The prevailing hypothesis is that the alveoli stop multiplying until 2-3 years of age, and then undergo a process of increase in volume and surface area, although some authors have suggested that alveolar formation may continue until 7-8 years of age, a process called neoalveolization⁽⁷⁾. 

Since lung development is a long-lasting phenomenon that begins in utero and continues at least until adolescence, in addition to genetic predisposition, many internal and external factors can interfere with lung development at multiple levels, including gene expression and epigenetics. Premature birth, bronchopulmonary dysplasia, maternal smoking during pregnancy, exposure to smoke after childbirth, early allergic sensitization, early viral infections and pollution may alter lung structure and metabolism. Thus, it is hypothesized that these early life events play a role in the pathogenesis of chronic obstructive respiratory diseases – bronchial asthma or chronic obstructive pulmonary disease. 

Smooth muscles and cartilage

The mesenchyme differentiates into smooth muscle at 6-8 weeks of gestation, while beta-adrenoreceptors appear at 14 weeks, and alpha-1-adrenoreceptors and muscarinic receptors appear after 23 weeks of gestation. The fetal bronchial smooth muscle has been shown to be able to contract spontaneously and respond to pharmacologic stimulation in a similar way to what occurs in adult smooth muscle. The only difference found between children and adults is that the mucous glands are proportionally more numerous in children⁽⁸⁾.

Thoracic cage

In newborns and infants, it has a pyramidal shape, the ribs have a typical horizontal orientation, and the thoracic cross-section is almost circular rather than oval. As younger children adopt an upright position, gravitational forces gradually begin to change the orientation of the ribs as well as the shape of the thoracic section. 

From a functional point of view, the horizontal orientation of the ribs makes it difficult for younger children to raise them in inspiration. Ventilation is mainly diaphragmatic, and the respiratory dynamics are less efficient. Moreover, in children, the ribs are mainly made of cartilage, which makes the rib cage flexible, further reducing the efficiency of the respiratory pump⁽⁹⁾. 

Lung elasticity changes during childhood. Some studies have shown that elastic recoil pressure increases with increasing height, age and body surface area, and this factor is particularly important, because small airways are not supported by any cartilage and their ability to remain patent depends on the elastic recoil of the lungs. Later in life, the lungs become stiffer due to collagen and elastin accumulations.

Respiratory muscles

In young children, the diaphragm has a horizontal position and is more flattened than in adults, giving it limited contractile capacity. The external and internal intercostal muscles are not well developed in children, especially in infants, and thus contraction of these muscles cannot contribute to the increase in anteroposterior and lateral chest diameters as in adults, and their contribution to respiratory effort and tidal volume is minimal. In the infant, the intercostals act to stabilize the more flexible chest wall, minimizing the inward displacement of the rib cage caused by the negative intrathoracic pressure produced by descending diaphragmatic contraction⁽¹⁰⁾.

In infancy, respiratory muscles are composed mainly of type II fibers (sensitive to fatigue due to lower glycogen and fat deposits), as type I fibers (resistant to fatigue) develop later in life. Greater susceptibility to fatigue of the ventilatory muscles occurs when respiratory rate is increased, especially in premature infants, who have the lowest percentage of type I fibers.

Conclusions

Therefore, at pediatric age, there are a number of anatomical and functional particularities of the respiratory tree: the resistance of the airways to flow increases, mucosal inflammation is more frequent due to the peculiarities of the immune system, the tracheal smooth muscle is more susceptible to trigger contraction, and mucus production is excessive.

Knowledge of the particularities of the pediatric airways is crucial in the prevention, management and treatment of acute and chronic pediatric respiratory diseases, and understanding the pathogenesis of pediatric respiratory diseases is closely related to the anatomophysiology of the airways. Tailoring therapeutic means to the age of the child and the pathogenetic pattern is essential for an effective medical action.

Autor corespondent: Bogdan A. Stana E-mail: bogdan.stana@gmail.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.