Kilic SS. Recurrent respiratory tract infection. Recent Advances in Pediatrics,Jaypee Brothers Medical Publishers, New Delhi, ISBN 81-8061-297-X , pp1-18, 2004

 

THE EVALUATION OF CHILDREN WITH RECURRENT RESP›RATORY TRACT INFECTIONS

Introduction

The young child who 'is always sick' is a common problem, creating concern for their parents and doctors. Pediatric respiratory tract infections are one of the most common reasons for physician visits and hospitalization, and are associated with significant morbidity and mortality. The diagnosis and management ofrecurrent respiratory tract infections (RTI) in children may present a significant challenge for the primary care physician. Timing, location, and prodromes to recurrence can all provide important clues to the etiology of infection. Children attending day-care facilities, having school-aged siblings at home, with atopy, crowding or exposure to cigarette smoke can have even more frequent infections.

Children experience 3-8 respiratory tract infections per year normally but 10-15% have at least 12 per year . The majority of children with recurrent respiratory tract infections are normal, however, it is important to consider atopy and underlying immunodeficiency 1,2. HIV infection is one of the commonest causes of secondary immnunodeficiency. However, frequent, self-limited viral infections in children attending day care or living in homes with older children, recurrent streptococcal disease or colonization, typically are not associated with antibody deficiency 3.

Additionally, children with protein, calorie, and vitamin malnutrition, mostly in developing countries, suffer from RTI.Defiency of vitamin Acan also cause recurrent infections of the respiratory and gastrointestinaltracts and lack of vitamin B12 can impair immunoglobulin production. Protein loosing clinical states such as protein-loosing enteropathies, intestinal lymphangiectasia and the nephrotic syndrome is associated with increased susceptibility to infections.

The role of physicians and other healthcare professionals has expanded from merely treating disease to implementing measures aimed at health maintenance and disease prevention.

Successful management of these patients depends on a careful evaluation of each episode, with a complete review of all available laboratory evaluation. This article provides an overview of diagnostic approach to children with recurrent RTIs for the evaluation of underlying pathology.

Defence mechanisms of respiratory tract

Respiratory defenses against infection involve a diverse and complex system. These defenses

include physiologic mechanisms, such as aerodynamic filtration and mucociliary clearance; reflexes, such as cough and brochoconsriction; immunoglobulins, protease inhibitors and other secretions; and phagocytic cells.

The first stage of defense against pulmonary infection depends on a favorable balance between entry of potentially pathogenic organisms and the hostís ability to clear microorganisms that access the respiratory tract. Mechanical barriers limit exposure of the respiratory tract to potential pathogenic organisms, whereas the mucociliary apparatus and cough reflexes work to expel any microorganisms that escape from the initial defenses.

Corruption of the anatomic and mechanical aspects of the respiratory tractís defense is one of the most common defects leading to infection. If these mechanisms malfunction (such as with structural or neurologic disease), the lower respiratory (which is normally sterile) is in danger of repeated exposure to aspirated contamined secretions from the pharynx 4,5 .

The epithelium in the nasopharynx, trachea, bronchi, and terminal bronchioles is composed of ciliated cells, covered by mucus. Ciliary movement propels overlying mucus toward the more central airways, creating a layer of mucus that moves up the respiratory tract. Kartagenerís syndrome is a primary ciliary dyskinesia which is characterized by dysfunction of the ciliary aparatus. The clearance of pathogenic organisms is impaired, facilitating the development of recurrent infections of the upper and lower conducting airways. Common respiratory pathogens, including viruses, Haemophilus influenzae, or Mycoplasma, are capable of elaborating ciliotoxic substances, which result in impaired ciliary function and diminished organism clearance and may contribute to develop infection. Acquired defects in mucociliary function may be related to toxic or infectious exposures. Defective mucus composition plays a key role in the repetitive infections that occur in patients with cystic fibrosis. Abnormal chloride composition in the mucus layer as well as increased viscoelastic properties can impede ciliary action, and bacterial killing.†††††††††

When microorganisms have gained entry to the lower respiratory tract, the alveolar macrophage and recruited phagocytes may eliminated these organisms. Pateints with phagocytic disorders are prone to infections by bacteria and fungi, although the spectrum of pathogens varies with different phagocytic disorders. These patients suffer from recurrent pneumonias as well as suppurative lymphadenitis, subcutaneous infections, and liver abscess often caused by a subset of catalase-producing pathogens such as, S.aerus, Serratia marcescents. Systemic diseases, including diabetes, sepsis, leukemias, and malnutrition cause to development of defective phagocytosis and subsequently pulmonary infection 6.

Ig A is the most prevalent immunoglobulin found in the secretions of the upper respiratory tract and plays a role in facilitating clearance of particulates and microbes. In the respiratory tract, antigen recognition leads to specific secretory IgA production locally at the mucosal surface.Patients with selective Ig A deficiency are at risk forrecurrent upper respiratory tract infection 7.

Risk factors for recurrent RTIs

The pediatrician must first determine whether these recurrent infections are because of host-derived factors or are the result of increased environmental exposure. Host-derived factors may be nonimmunological or related to host immunodeficiency. The leading cause of recurrent respiratory tract infections throughout the world is increased environmental exposure in children attending nursery school or daycare centres. Environmental factors that increase the risk include group child care, number of hours in child care, exposure to children at home or in child care, number of smokers and cigarettes smoked in thehousehold, feeding in the supine position, autumn season and shorter duration of breast feeding. Maternal smoking during pregnancy and postnatal passive exposure predispose the children of smokers to recurrent respiratory infections. Young children in day care or those exposed to tobacco smoke can have as many as 10 episodes of infection over 1 year, even with a healthy immune system 8,9 . Host-derived risk factors which cause recurrent pneumonias usually result from deficiencies in the local pulmonary or systemic host defences or from underlying disorders that modify the lung defences. The underlying disorders associated with recurrentrespiratory tract infections are congenital malformations of the upper or lower respiratory tract and cardiovascular system, recurrent aspirations, defects in the clearance of airway secretions, especially cystic fibrosis and ciliary abnormalities, and disorders of systemic and local immunity. In children with onset of symptoms at an early age, structural or functional anomalies of the airway or the lung are important causes such as tracheo-oesophageal fistula or sequestration .

Factors associated with recurrent pneumonia in developed countries include foreign body aspiration, asthma, immunodeficiency and pulmonary anomalies 10,11 .

Jedrychowski et al 12 studied that the predisposition to acute respiratory infections among overweight preadolescent children. They found that the susceptibility to acute respiratory infections was related significantly to body mass index, allergy and environmental tobacco smoke. Central heating in the household was shown to have a protective effectwhen compared with children from households where coal or gas was used for home heating.

Etiology and Epidemiology

Acute respiratory infection is a leading cause of mortality among children younger than 5 years of age in developing countries, accounting for ~4 million deaths annually 13 . The incidence rates for pneumonia in developing countries are up to 10 per 100 children per year.A subgroup of these children suffers from recurrent pneumonia which has been defined as two episodes of pneumonia in 1 year or more than two episodes during any time frame. The vast majority of acute upper respiratory tract infections are caused by viruses, such as rhinoviruses, coronaviruses, the respiratory syncytial virus, influenza and parainfluenza, and adenoviruses. Recurrent viral infections are part of the growing up process of any child. Although their immune and respiratory defences are normal, many of these children are simply having the repeated viral respiratory tract infections.S. pneumoniae, H. influenzae, M.pneumoniae, C. pneumoniae, and M. catarrhalis are the commonest non-viral pathogens for lowerrespiratory infections 14. In many cases, no pathogen can be identified.

Overview of respiratory tract infections

Upper respiratory tract infections:

Upper respiratory tract infections (URTI) including nasopharyngitis, pharyngitis, tonsillitis and otitis media constitute 87.5% of the total episodes of respiratory infections. Recurrent throat problems in children are common and have an impact on the family. Time off school, or parental time off work was significantly associated with parental worry and distruption 15.

The cause of URTI are multifactorial (enlarged adenoid, environmental conditions, staying at the care centers, smoking parents, allergy). Directly, viral infection causes damage to the ciliary cells and mucociliary clearance. Enlarged adenoids reduce ventilation to the nasopharynx, increase accumulation of the secretion and provide a good condition for bacteria. Allergy is confirmed in 35-38% of URTI children 2,16 .

The vast majority of acute upper respiratory tract infections are caused by viruses. Recurrent viral infections are part of the growing up process of any child. Although their immune and respiratory defences are normal, many of these children are simply having the repeated viral respiratory tract infections. Common cold is caused by viruses in most circumstances and does not require antimicrobial agent unless it is complicated by acute otitis media with effusion, tonsillitis, sinusitis, and lower respiratory tract infection. Most instances of rhinosinusitis are viral and therefore, resolve spontaneously without antimicrobial therapy. The most common bacterial agents causing sinusitis are S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus and S. pyogenes. Acute pharyngitis is commonly caused by viruses and does not need antibiotics. About 15% of the episodes may be due to Group A beta hemolytic streptococcus (GABS) 17.

Acute otitis media in children is of particular concern because of its high incidence, frequent recurrence, and serious long term sequelae, e.g. hearing loss. Middle ear infections are the reasons for up to 30% of pediatric office visits. The peak incidence occurs between seven and nine months of age. About 17% of all children under two years old have recurrent ear infections (ie, three or more episodes within a six-month period). Children from lower socioeconomic groups have a higher incidence than do those who live in wealthier communities.Babies who are bottle-fed may have a higher risk for otitis media than do breast-fed babies because the mother's milk provides immune factors that help protect the child from infections. Onset of otitis media during the first few months of life, bilateral otitis media, male gender, prior otitis media episodes, and having a sibling with an otitis media history have been implicated in increasing the risk of recurrent otitis media (ROM). The most important predictors of ROM are respiratory tract infection, early entry into group day care, hours spent in day care, supine feeding, having older sibling and shorter duration of breast feeding18,19.

Other disorders and infections of the airways in the upper and lower respiratory passages, such as asthma and sinusitis, parallel the rise in ear infections. It is well recognized that adenoid hypertrophy and allergic rhinitis are common in these children. Efforts should be made to diagnose and treat manifestations of hyperactive airway or allergy in these patients group.

In children, sinusitis is a common, generally uncomplicated, and self limiting disease which decreaseswith age. The diagnosis is difficult because of relatively non specific signs and symptoms that overlap with viral upper respiratory infection and allergy. Viral illness appears to be the most common predisposing factor. The most common bacterial pathogens in pediatric sinusitis patients are Streptococcus pneumoniae, Hemophilus influenza and Moraxella catarrhalis. Other less frequent bacterial species include group A streptococcus, group C streptococcus, streptococcus viridans, peptostreptococcus, and moraxella species. Respiratory anaerobes are not common. An immunologic screening should be extended to patients who have persistent sinus infection, despite normal mucocilary and ventilation patterns, inadequate response to antimicrobial therapy, culture of unusual pathogens from the upper respiratory tract or history of infection at other side, mainly bronchopulmonary. Immune defects (mainly IgG2 and IgA) may exist in a significant percentage of children . The role of allergy seems less important 17, 20. With advances in the genetic field of cystic fibrosis, genetic factors are advocated in chronic or recurrent sinusitis.

Lower respiratory tract infections:

Pneumonia is one of several infections of the lower respiratory tract that may be observed in children. The other lower respiratory tract diseases, croup (laryngotracheobronchitis), bronchitis, and bronchiolitis (to which pneumonia is closely related), are beyond the scope of this article and are not discussed further.A peak incidence for pulmonary infections is at the end of the first year. There is no community reports on the incidence of recurrent pneumonia, but the overall hospitalization rate for pneumonia has been reported as 16 per 1000 children per year in 5-14 year olds. The age and sex influence the frequency of respiratory infection. Two-thirds of childhood deaths due to respiratory infections occur in infancy. Pulmonary infections are common in boys more than girls 21. All children with normal immune function will make a full recovery from pneumonia or bronchiolitis, even if the acute episode was severe. However, adenovirus serotypes 3,4,7 and 21 can all cause severe bronchiolitis, pneumonia and death. Most of survivors have permanent damage to the airways such as bronchiolitis obliterans, atelectasis, bronchiectasis 22,23. Whatever the underlying cause, the inflammatory response leads to increased neutrophil activity and the release of inflammatory mediators into the tissue. This process eventually leads to the leakage of plasma and oxidative enzymes into the surrounding tissue. The result is loss of surfactant activity with local collapse and consolidation.

Similar damages can develop following severe mycoplasmal pneumonia. These patients commonly have persistent wheezing, cough and productive sputum. Although most children make a full recovery from bacterial pnemonia, in some have persistent clinical symptoms and pathologic radiologic findings such as atelectasis, inflammation caused bya mucopus plug or localized damage to the bronchus.

Clinical clues to diagnosis include recurrent infections at other locations and failure to thrive in the cases of an immune disorder, recurrences involving the same location in those with underlying pulmonary pathology, the association of respiratory symptoms with feeding in those with gastroesophageal reflux, or recurrent wheezing in asthmatic children. Recurrent pneumonia mostly occurs in children having a known predisposing factor included oropharyngeal incoordination with aspiration syndrome, immune disorder, congenital cardiac defects, asthma, pulmonary anomalies, gastroesophageal reflux 24 . The assessment and management of children with recurrent pulmonary infections requires detailed and specialist assessment. It needs the cooperation of several disciplines, including respiratory pediatrician, pediatric immunologist, radiologist, microbiologist and physiotherapist. However, physcians should bekept in their mind that repeated respiratory symptoms do not always mean a respiratory infection.

Gastro-esophageal reflux

Gastro-esophageal refluxis the major cause of recurrent aspiration. In infants, gastroesophageal reflux disorder (GERD) may occur when muscles in the upper part of the stomach are still immature and force acid back up, causing persistent vomiting. GERD is manifested as epigastric discomfort, regurgitation, and vomiting. Not uncommonly, respiratory disorders are the only presenting findings in reflux patients. Some research also suggests that GERD in infants may contribute to respiratory tractinfections by triggering inflammation in these upper passages. GERD usually causes asthma symptoms and aspiration pneumonia. An estimated incidence of GERD in asthmatic patients may range from 34% to 89%. Bronchoconstriction induced by reflux usually occurs at nigt when the esophageal acid clearance is delayed. Rhinosinusitis, stridor and croup may manifest secondary to inflammatory changes and swelling within the airway from gastric reflux exposure 25,26.

Cystic fibrosis

The prevalence of cystic fibrosis (CF) occurs in 1 in 2500 births in Caucasians. Affected children present with chronic upper and lower respiratory infections. Other manifestations include malnutrition, pancreatic insufficiency, and intestinal obstruction. Although elevated sweat chloride concentrations are the hallmark ofCF diagnosis, the detection of specific genetic mutations is more reliable method of diagnosis. Obstruction of airways by mucus predisposes to pulmonary infections. The lungs are usually colonized with S.aureus and P. aeruginosa. Progressive lung involvement is manifested by chronic productive cough, recurrent pulmonary infections, lung abscesses, bronchiectasis, cysts, cor pulmonale and acute and chronic respiratory failure, which eventually terminate in a premature death. Atelectasis, hemoptysis, and pneumothorax are the typical complications 27,28.††

Tracheobronchial foreign bodies

Tracheobronchial foreign bodies are most commonly aspirates during the toddler years, ages 1 to 3.These children are ambulatory and may be out of parental view during the acute aspiration incident. It has been reported that up to 50% of patients with foreign body aspirations do not have a contributing history available. The clinical presentation of acute airway obstruction associated with a foreign body aspiration is a brief period of choking, gagging, or wheezing. This may be associated with hoarseness, aphonia, or dysphonia. For infants less than 1year of age, back blows and abdominal thrusts are recommended. The second peak occurs between ages 10 and 11. The Heimlich maneuver is reserved for older children or adults. The most common clinical trial for patients with a bronchial foreign body includes cough, wheezing, and decreased breath sounds. The resulting symptoms may mimic intermittent tracheobronchitis, recurrent pneumonia, or asthma. These children may be treated with antibiotics and steroids, which may mask symptoms and delay further the diagnosis. For this reason, in children with atypical or prolonged pulmonary symptoms the possibility of a foreign body should be raised. Delayed complications associated with a retained foreign body include pneumonia, obstructive emphysema, and brochiectasis. Many foreign bodies are not radiopaque and small foreign bodies may cause symptoms but not radigraphic changes. Plain films may be inadequate to document a nonradipaque foreign body unless they are obtained in the expiratory phase. On expiration air trapping, obstructive emphysema, and a mediastinal shift may be demonstrated by fluoroscopy or decubitus film. The possibility of granulation tissue and post-obstruction infection exists after removing a retained foreign body 29,30.

Asthma

Asthma is characterized by a recurrent episodes of cough, wheeze and breathlessness, which is triggered by upper respiratory infections, aero-allergens, cold air and exposure to pets. There is usually a personal or family history of atopic illness. Patients with humoral immunodeficiency such as Ig A deficiency and/or Ig G subclass deficiency have an increased risk for RTI or asthma. Bronchodilators or anti-inflammatory drugs are the mainstay of asthma therapy.††††

Immunodeficiency disorders

The presence of recurrent infections other than pneumonia and opportunistic infections are important clues to immunodeficiency. The age of presentation, the type of organisms involved, the family history is a helpful indicators for likely diagnosis. A diagnosis based on laboratory, molecular, or genetic criteria allows optimal therapy and genetic counseling.

Comprehensive medical and family history taking is essential in the evaluation of patients with suspected imunodeficiency disorders. It should focus on recurrent, severe, and unusual infections and evidence of failure to thrive in childhood. A family history of fetal wastage and infant deaths caused by infections in siblings and in the extended family is suggestive of immunodeficiency. Additionally, a history of repeated infections requiring antibiotic therapy, or poor response to antibiotic therapy with continued symptoms, could be associated with immunodeficiency. In the evaluation of immunodeficency, other possible causes should be considered, such as malnutrition, occult malignancy, and treatment with steroids or other immunosuppressive drugs. Repeated upper and lower respiratory tract infections, particularly with gram-positive (pneumococci, staphylococci, streptococci) and some gram-negative encapsulated (Haemophilus sp.) bacteria, develop in follow-up period. These infections typically are accompanied by severe complications of routine infections (e.g., chronic otorrhea, mastoiditis, brain abscess, and empyema) in immunodeficiency patients 31.

Children with recurrent infections significant enough to warrant referral to an immunologist frequently have abnormalities of the humoral immune system. The spectrum of antibody deficiencies ranges from severe deficiencies of all immunoglobulin isotypes (agammaglobulinemia) to milder but clinically relevant deficiencies of specific antibodies in patients with normal imunoglobulin concentrations. The immune system is not completely mature at birth and may not be well developed in some aspects until a child reaches school age.

The most common abnormality is partial IgA deficiency. The prevalence of Ig A deficiency in healthy individuals varies from 1:396 to 1:2170. These patients are at risk for recurrent upper respiratory tract infection. Some gram negative bacteria (P.aeruginosa, E.coli, Serratia, Proteus, and K.pneumonia) have the capacity to destroy secretory Ig A. Loss of Ig A has been correlated with accentuated bacterial mucosal adherence, colonization and subsequent respiratory infection. The concomitant association of one or more Ig G subclass deficiencies seems to predispose patients to more severe and frequent infections. Recurrent upper and lower respiratory tract infections, particularly with gram positive and some gram negative encapsulated bacteria, develop in patients with humoral deficiency syndromes.Pneumonia complicated by multilobar involvement ultimately can lead to bronchiectasis in these patients such that early diagnosis of an immunodeficiency becomes an important management issue.††† Repeated determination of Ig A, Ig G sublasses and specific functional antibody evaluation should be performed in order to discriminate between a transient antibody deficiency due to a delayed maturation of the immune system and a primary humoral immunodeficiency.

Ig G replacement therapy is usually considered when the patient shows evidence of chronic infections and immunodeficiency and fails to respond to other therapies. Prolonged follow-up of these patients is mandatory to promptly detect the number of defects that could evolve in more severe immunodeficiencies 32- 34. Additionally, recurrent pneumonia is also commonly seen in children with the acquired immunodeficiency syndrome 35. Lymphocytic interstitial pneumonitis is the most common respiratory complication of pediatric HIV infection.

Pharyngeal incoordination in children with neurologic disorder is often caused to recurrent pulmonary infections. Disorders of ciliary function, congenital abnormalities of the lung and tuberculosis should also be considered in any child with recurrent and persistent chest infections.

Medical and Family History

Diagnosis depends on taking a detailed history, detecting any abnormal physical sign, and the use of appropriate tests. The differentiation between patients who have infecions caused by an immunodeficiency syndrome and those who have recurrent RTIs caused by other predisposing factors, such as structural abnormalities, allergic diseases, or cystic fibrosis, requires taking a careful medical history, physical examination and diagnostic studies. It is also important to note that the frequency, duration, severity, and complications of infections and the response to antimicrobial treatment while taking history.A history of persistent or recurrent episodes of pneumonia andchronic sputum production indicates more severe pathology. Persistent cough at night or after getting up in the morning suggests the presence of chronic lung disease and bronchiectasis 36.A detailed family history in patients in whom immunodeficiency is suspected can add valuable information. Medical history taking should include information about any adverse reaction to live viral vaccines.

Physical examination

The initial assessment should include the general appearance of the patient. Patients having severe, recurrent infections present with failure to thrive; are often pale, irritable. Absence of tonsillar tissue in the oral cavity or lymphoid tissue in the head and neck examination is often associated with B lymphocyte deficiencies. Examination of the pharynx and nasal cavities for signs of sinusitis, including postnasal drainage, purulent nasal discharge is important. An otoscopic examination of a child should form part of a pediatric examination in all cases of respiratory infections. Rales on auscultation on the chest may suggestbrochiectasis developed as a complication recurrent pulmonary infections. Pulmonary hypertension and digital clubbing points to chronic lung disease 37.

Laboratory evaluation

The diagnostic tools available range from simple, routine laboratory tests to complex immunologic and genetic procedures. Investigations are needed in recent lower respiratory infections to disclose adverse effects of infections on growth, school performance, and physical findings. A complete blood count with differential should be analysed first. The absolute numbers of neutrophils and lymphocytes should be noted and interpreted according to age-appropriate normal numbers.Anemia of chronic disease can develop in patients with chronic infections. CRP (C-reactive protein), ESR (erythrocyte sedimentation rates), nasal smear, appropriate cultures, viral and mycoplasmal antibody levels, tests for tuberculosis,X-Rays, barium studies, ultrasound, echocardiography, esophageal pH manometry,CT (computerized tomography), HRCT (high resolution computerized tomography), MRI (magnetic resonans imaging) in selected cases. Specialist investigations including sweat tests, ciliary function tests, immunologic tests laryngoscopy and bronchoscopy are often indicated in children with suppurative lung disease.

Immunological evaluation:
Immune responses are traditionally classified as innate (nonspecific) and acquired (specific). The innate immune system consists of phagocytic cells, the complement system, and selected cytotoxic cells. Pateints with phagocytic disorders are prone to infections by bacteria and fungi, although the spectrum of pathogens varies with different phagocytic disorders. The complement proteins play an important role in innate immunity, promoting inflammation and microbial killing. They play a role in the adaptive immune response, as well.

The adaptive response is initiated by lymphocytes encountering foreign antigen and depends on a combination of cell-cell interactions that generate humoral mediators, including immunoglobulins or cytokines that modulate the response. Antibodies, an essential component of host defense, attach to infecting microorganisms, enhancing opsonization for phagocytosis. Antibodies are effective against extracellular pathogens, such as Staphylococcus aerus, Haemophilus influenzae, Streptococcus pneumonia, and Neisseria meningitides, and viruses before intracellular infection occurs. Cellular immunity is essential against intracellular pathogens, including viruses, mycobacteria, salmonella, fungi, Pneumocystis carini and Toxoplasma gondii. Particular elements of the immune system play a specific role in host defense, and their close interactions with each other render adequate protection to the host 38.††††

Abnormalities leading to immunodeficiency diseases can be broadly classified as defects of the a) humoral system, b) hŁcresel system, c) complement system, and d) phagocytic system.

Defects involving humoral immunity are the commonest immune abnormalities, accounting for more than 50% of the recognized causes of primary immunodeficiency. Combined cellular and humoral deficiencies constitute 20% to 30% of all cases, followed by phagocytic defects, at 18%, and complement deficiencies, at 2% .

Although the possibility of an immunodeficiency should be considered in any individual with frequent infections, these are relatively uncommon disorders. Most of non-immunological causes of recurrent infection can be readly suspected after a careful history and physical examination and can be confirmed by appropriate laboratory tests. Prime candidates for evaluation of the immune systems are infants born to families known to have members with immunodeficiency, patients with recurrent infections that fail to respond appropriately to antibiotics, children who present with failure to thrive, suffer from diarrhea or interstitial pneumonia, or present with opportunistic infections or recurrent skin infections, poor wound healing, cold staphylococcal abscesses, periodontitis 39.

The evaluation of the humoral immunity starts with the measurement of serum immunoglobulins. When assessing serum immunologlobulin concentrations, physicians should consider the developmental changes in immunologlobulin levels occuring from infancy to adolescence. If the immunoglobulin levels are low, decreased production and loss through the gastrointestinal tract or renal tract should be considered. Serum albumin levels can serve as an indirect measure to differentiate these disease. Immunologically healthy children who experience frequent infections are likely have high immunoglobulin levels; therefore, low or borderline immunoglobulin levels in patients with proven frequent infections suggest immunodeficiency. The measurement of Ig G subclass concentrations needs consideration. A key element in the evaluation of humoral immunity is the determination of a patientís ability to produce specific antibodies to a microorganism or its products. Evaluation of the antibody response to potein and polysaccharide antigens is necessary. Diphteria and tetanus toxoids, and multivalent S. pneumoniae polysaccharide vaccines are readily available immunizing agents. B cell enumeration is unnecessary unless a profound abnormality in immunoglobulin levels is estabilished. The assessment for immune dysfunction always should include testing for possible HIV infection. Delayed hypersensitivity skin test can serve as an initial screening test of T-cell immunity. If initial screening tests show abnormal results, the child should be referred to a clinical immunologist for further evaluation. Cooperation between clinical immunologist and pediatrician should be warranted for providing primary care to these children. Prompt recognition of infection and aggressive treatment are essential to aviod life-threatening complications and improve the life quality 3,32-34.

HOW ARE RECURRENT RESPIRATORY INFECTIONS IN CHILDREN PREVENTED?

Parents or others should not smoke around children. If possible, new mothers should breast feed their infants for at least six months. Simple precautions for prevention of colds are eating plenty of fruits and vegetables, getting enough rest, and washing hands frequently. New antibacterial soaps add little protection and ordinary soap is sufficient. In fact, a recent study suggests that common liquid dishwashing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia.

Vaccines

Children who are susceptible to recurrent respiratory infections should probably also be given vaccinations against influenza viruses and pneumococci. The influenza vaccine must be given every fall to protect against the current year's specific flu strain. The pneumococcal vaccine (23-valent pneumococcal polysaccharide vaccine), which is used against Streptococcus pneumoniae, provides protection for many years, and some experts now recommend if for children with recurrent infections who are over two years. While most of young, healthy children has been found to be immunogenic in pneumococcal vaccine,a significant percentage of children with recurrent sinopulmonary infections fail to produce adequate serotype specific antibodies following pneumococcal immunization 40.
A newer pneumococcal vaccine (Prevnar) has been shown to reduce respiratory infections by 7%. Researchers are developing antibodies directed against the proteins P6 and Hin47 which compose the outer membrane of Haemophilus influenzae. A vaccine targeted against the Hin47 protein is now in clinical trials 41, 42.
Additionally, immunotherapy has been proposed as a means of preventing these recurrent infections by providing children with small doses of inactive bacterial antigens liable to trigger specific and protective immune responses. Among such drugs, ribosomal preparations appear to be not only well tolerated, but also ideally targeted to induce mucosal responses. One preparation of ribosomal mucosal vaccine is commercially available in several countries. Numerous clinical trials in the world have confirmed the positive role of this mucosal ribosomal bacterial vaccine in significantly reducing the number of infections, courses of antibacterials. In vitro and ex vivo investigations have confirmed that such vaccines indeed trigger protective specific immune responses 43-44.
Treatment

Rational approach to diagnosis and management of recurrent respiratory infections is needed, or else the child is subjected to unnecessary investigations and multiple drugs. Prompt recognition of infection and aggressive treatment are essential to avoid to life-threatening complications and improve prognosis. Initiation of early empiric coverage for suspected pathogens after obtaining appropriate cultures. Antibiotics should be judiciously chosen depending on age, socioeconomic status, severity of infection and the type of organism expected and always given in adequate doses and proper duration. Children at highest risk for developing resistant bacteria are those who have failed previous treatments, have had numerous previous antibiotic prescriptions, or received low doses of antibiotics over a prolonged period. Preventive antibiotics are usually given to children who have at least three episodes of RTIs within a six-month period. Physician opinion varies as to the best timing for these antibiotics. They may be given for a consistent three- to six-month period following the last acute episode. Some physicians may prescribe them only in winter and spring when the risk for respiratory infections is high. The preventive regimen is one or two daily doses of amoxicillin or sulfisoxazole. Patients with B cell immunodeficiencies who continue to experience recurrent infections despite intravenous immunoglobulin replacement treatment also should be considered for concomittant antibiotic therapy to avoid complications, such as chronic lung disease and bronchiectasis.

Recurrent infections may predispose children to poor weight gain and growth; therefore, monitoring of the height and weight should be performed frequently and appropriate nutritional interventions initiated early if problems arise. Recent approaches have included the encouragement of breastfeeding, and respiratory syncytical virus immune globulin, as well as methods of stimulating immunity, such as ribosomal immunotherapy.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Summary and Conclusion
Pediatric respiratory tract infections are one of the most common reasons for physician visits and hospitalization, and are associated with significant morbidity and mortality. Acute respiratory tract infection is a leading cause of morbidity and mortality among children younger than 5 years of age in developing countries. Children, daycare attendance, crowding or exposure to cigarette smoke are predisposed to recurrent respiratory infection. Congenital defects in either the function or the structure of the cilia predispose the host to defective tracheobronchial clearance and recurrent respiratory infections. Recurrent RTIs are not always indicative of an abnormality in immune system functions. A thorough history and physical examination focused on severity, sequelae, and microbiology of infections can usually determine whether a patient needs further evaluation. Multidiciplinary approach is necessary in these patients for diagnosis and follow-up. The early and successful management of recurrent RTI in children relies on careful diagnosis, recognition of causative factors, and judicious yet appropriate antimicrobial and ancillary medical therapy.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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