Tuesday, April 2, 2013

BRONCHOPULMONARY DYSPLASIA (BPD) IN CHILDREN

In recent years increasingly relevant bronchopulmonary dysplasia (BPD).
              BPD is acquired chronic obstructive pulmonary disease that develops as a result of respiratory distress syndrome of neonates and / or artificial ventilation (AVL) with high concentrations of oxygen, accompanied by hypoxemia, altered reactivity of the bronchi with hypersensitivity of airways, and typical radiological changes.
              In the etiology of BPD there are many factors: the impact of oxygen in high concentrations, mechanical ventilation, pulmonary edema, left to right shunt at patent ductus arteriosus, recurrent bacterial pneumonia, hereditary predisposition, hypovitaminosis A and E.
                             Pathological Anatomy and Physiology
                     According to the results of postmortem studies, there are 4 stages of BPD, which are similar to roengenologic findings. In the first three days of life (I stage), there is a typical respiratory distress syndrome. In the following days the first week of life (II stage) there are destruction of cells of the alveolar epithelium and capillary endothelium, interstitial edema and perivascular space, necrosis of the bronchioles, squamous metaplasia, hypertrophy of smooth muscle cells of the disappearance of ciliated epithelium. In the II-III week (III stage) there is increasing of the number of macrophages and plasma cells and fibroblasts. Process damage the bronchial tubes of different orders, which in severe cases leads to obliterative  bronchiolitis. In the following week atelectasis zones with interstitial and peribronchial fibrosis in conjunction with areas of emphysema (IV stage) are revealed. In the walls of the alveoli there is increasing of the number of reticular, collagen, elastic fibers, which structure is disrupted.
                 Naturally pulmonary emphysema develops caused by three mechanisms: 1) scars that appear due to hyperextension of nonfibroid lung; 2) violation of the multiplication of alveoli in some areas (atrophic form of emphysema); 3) destruction as a result of the inflammation and destruction of the walls of the alveoli and capillaries. Structural changes of the pulmonary arteries include intimal proliferation, smooth muscle hypertrophy, the proliferation of smooth muscle on the distal parts of vessels, thickening and fibrosis of the adventitia, the decreasing of diameter of the arteries.

             In diagnosing BPD anamnestic data are important:
·        prematurity
·        birth weight less than 1500g
·        RDS in the first hours of life
·        ALV with rigid parameters for more than 6 days
·        oxygen dependance at least 1 month.

                                  Clinic:
            Specific clinical manifestations of BPD are absent. The clinical picture of BPD symptoms is presented with chronic respiratory failure (tachypnea to 80-100 per minute, cyanosis, emphysema, rib retraction, persistent physical examination changes in the form of an elongated exhalation, dry wheezing, moist small bubbling rales, stridor is possible) in preterm infants who are dependent on high concentrations of oxygen in inhaled air and mechanical ventilation for a longer or shorter time.
           Resistant respiratory failure develops after the initial improvement under AVl. This dependence on oxygen and mechanical ventilation may be manifested in different ways.
           The diagnosis of BPD brings together a wide range of clinical manifestations and changes on the radiograph. In mild cases may be observed only the impossibility of reducing the oxygen concentration and the parameters of artificial ventilation for 1-2 weeks, lengthening the period of recovery from respiratory failure. In severe cases in the background of AVL hypoxemia, hypercapnia remain, "remove" a child from a ventilator is impossible within a few months, reintubations are characteriatic. Typically, the suspicion of BPD occur when the child needed mechanical ventilation, especially with positive end-expiratory pressure, for more than 1 week. Cough, persistent symptoms of bronchial obstruction syndrome in patients are preserved  on already spontaneous respiration.
           Further, after the neonatal period, course of BPD is wavy, depending on the degree of morphological and functional disorders. The majority of patients showed a slow but clear improvement and normalization of the state in 6-12 months, but in some patients violations persist for a long time. According to observations GM Dementieva et al. (1997) at 16-20% of children discharged from office for prematurity, pathological changes in the lungs retained and in older age - for 1-4 years of life, and 4% of patients BPD in the future lead to disability. Recovery in children with BPD may be due to the fact that along with the fibro-proliferative processes in the lungs of preterm there is occurring regenerative process and continuing growth and development of the lungs.
         Examination reveals the cough and persistent physical examination changes, the increasing of obstructive disorders at virus infection, the symptoms of latent respiratory insufficiency detected by the load - sucking, moving, crying, while often develop pulmonary heart at an early age, neurological disorders, retarded physical development. The final diagnosis is established after the radiographic examination with signs of fibrosis in the form of deformation and strengthening of local lung pattern or a light disguise lung fields in middle medium sections, alternating with areas of swelling of lung tissue, primarily in low lateral areas in children older than 1 month.
Roentgenography of child 5 mths with BPD  

           Activities for the prevention of BPD include:
1. Pharmacological acceleration of lung maturation: prenatal prevention of RDS accelerates the maturation of surfactant synthesis and is one of effective methods of reducing the frequency and severity of BPD. Birth of a baby without the RDS  gives possible to avoid mechanical ventilation, and consequently, the mechanical (positive pressure) and chemical (oxygen) injury of the lungs. One of the most common methods of prenatal prevention of RDS is the GCS therapy, which stimulates the synthesis of surfactant in the lungs of the fetus.
2. Rational etiopathogenic therapy of RDS: in preterm infants it involves the use of exogenous surfactant preparations that can achieve the reduction of severity and reducing the duration of the disease and, consequently, the duration of mechanical ventilation and oxygen therapy in general.
3. Selection of the optimal level of respiratory support of  child: currently there is no doubt that the early onset of respiratory care can reduce its duration and limit the softer options like the pressure and the oxygen content. Early spontaneous respiration under constant positive pressure of (SRCPP) makes it possible to limit the scope of respiratory care, stop the progression of RDS and avoid the need for mechanical ventilation.
               At mechanical ventilation it should be strive to limit the minimal sufficient level of peak pressure and minimal sufficient concentration of oxygen. A special problem is a return the child from mechanical ventilation to spontaneous respiration. This is a long process, involving a slow decrease in ventilatory parameters, transfer the child to SRCPP through endotracheal tube, and then - through a nasal cannula.
4. Proper maintenance of water balance and energy supplementation: control of water balance is reduced to restrict fluids to 90% of fluid consumption. Excessive hydration leads to the pulmonary edema and disorders of gas exchange.
              Already in the early stages of BPD children need increased energy supply. Parenteral nutrition in the first days of life is intended to prevent catabolic processes. The full parenteral providing of proteins, carbohydrates, fats, vitamins and micro elements is important to limit further damage to the lungs and create conditions for their repair.
              In children with already established BPD in terms of water balance, their treatment has a number of perculiarities. Children with BPD have little resistant to the normal amount of fluid and tend to accumulate it in their lungs. They have  problems with nutrition, manifested in an imbalance between the demand of food and limitation of fluid. Often grows retardation occurs, so callories  should be increased, due to immaturity, growth need, increased work of breathing, high levels of metabolism (the additional cost of the energy supply of the inflammatory reaction). In order to achieve normal growth and development there must be at least 120-150 kcal / kg per day.
5. Supply of antioxidant protection. There is the immaturity of enzyme mechanisms in preterm infants. Animal studies and human biological material confirm the effectiveness of superoxide dismutase and catalase, the result of which is manifested decreasing of cell damage, increasing survival, and possibly the prevention or reduction in the severity of barotrauma. Today GCS are used n the postnatal period, not only for prevention of BPD, but for treatment of already formed disease.

                            Therapeutic activities:
1. System GCS stabilize cellular and lysosomal membranes, increases surfactant synthesis, increases the concentration of vitamin A in serum, inhibit prostaglandins and leukotrienes, reduce swelling of lung tissue and improve microcirculation in it. Currently, there is intensive studing of the role of inhaled GCS (beclomethasone, budesonide, flyuticazon) as an alternative to systemic GCS, or as a component of systemic steroid therapy. The available data are contradictory: some researchers prefer inhalation dexamethasone, others do not confirm the benefits of its application.

   
Flixotide
    

                    Steroid therapy involves two options: early administration of steroids prevents the formation of BPD (late first - early second week of life when on the background of persistent pulmonary edema appears interstitial emphysema) and  treats already established BPD (from the second month of life). Routine use of dexamethasone in the treatment of BPD is not currently recommended because of the many negative side effects. Its appointment is justified only when there is extreme severity of pulmonary symptoms.
2. Inhaled β2-adrenomimetics also found their application in the treatment of BPD. Salbutamol is a specific agonist of β2-receptors and currently enjoys high popularity in the treatment of BPD. Thanks bronchodilatory effect it reduces bronchial resistance and increases the permeability of the bronchi. However, since the first weeks of life expressed relaxation of smooth muscles of the bronchi is absent, early salbutamol inhalation therapy is not considered justified.

3. Systemic bronchodilators, which are the most commonly used in the treatment of children with BPD, include methylxanthines - aminophylline, theophylline, caffeine (more rarely).

  
4. Pulmonary vasodilators: nifedipine (calcium channel blockers). A single oral dose of nifedipine (0.5 mg / kg) reduces vascular resistance in the lungs and increases cardiac output in older children with severe vascular hypertension due to BPD.
5. Antibiotic: A number of studies in recent years distinguished Ureoplasma urealyticum as a factor contributing to the development of BPD. The results of clinical trials demonstrate reduction in the severity of the disease during therapy with macrolides.

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