Often a Sick Child: When to Start Worrying
Assoc. Prof. Laimutė Vaidelienė
LSMU Children’s Diseases Clinic
Many children, once they start attending group settings, often become ill. Frequent respiratory tract infections are usually caused by an immature immune system, anatomical and physiological peculiarities of the child’s body, and social factors. These children often have chronic infectious foci in the nasopharynx and are frequently diagnosed with allergies. It is important for the physician to distinguish whether frequent infections are not a sign of a serious chronic respiratory disease, because the course of most chronic lung diseases greatly depends on early diagnosis and timely treatment.
When examining frequently ill children, it is important to rule out the most common causes of recurrent respiratory illnesses: recurrent viral infections, chronic infectious foci in the nasopharynx, allergic diseases (bronchial asthma and allergic rhinitis), and gastroesophageal reflux disease (GERD). In addition, it is necessary to determine whether the course of respiratory tract infections is normal, whether the treatment provided was appropriate, how the child feels during remission, and whether the child is developing normally. If the illnesses can be described as severe, persistent, unusual, recurrent, or caused by unusual pathogens, and if there have been severe chronic diseases or early deaths in the family, such children must be examined for possible rare chronic diseases, such as suppurative lung diseases, chronic infections, anatomical defects of the respiratory tract, and immunodeficiencies.
Unfortunately, there are currently no reliable, evidence-based research and diagnostic methods for all possible clinical cases, so we hope that the general recommendations based on the experience of internationally recognized specialists presented in this article will be useful for practicing physicians.
Introduction
Every family doctor caring for children encounters frequently ill children. Respiratory tract (RT) infections are the most common pathology in children and one of the most frequent reasons for seeking medical attention. About 25% of infants and 18% of children aged 1–4 years suffer from recurrent respiratory tract infections [1,2]. These diseases account for 75% of all prescribed medications, with antibiotics being the most commonly prescribed. According to a study by G. Urbonas, antibiotics are prescribed in up to 40% of cases during the first visit when treating acute viral RT infections [19]. This is done because of pressure from parents, an inability to observe the patient, an attempt to protect against severe bacterial infections, and the inability to perform diagnostic tests such as blood tests and CRP. However, in many cases these are common, uncomplicated, although sometimes frequently recurring, viral respiratory tract infections, for which antibacterial treatment is irrational and unjustified.
Therefore, it is crucial to identify the individual causes of frequent RT infections in children, assess risk factors, and provide appropriate treatment as early as possible. If treatment is ineffective, the child should be referred for specialist consultation.
Factors Influencing Frequent Childhood Respiratory Tract Infections
The frequency of respiratory tract infections depends on various factors, primarily the maturity of the immune system and the anatomical and physiological characteristics of children’s respiratory tracts.
Anatomical and physiological features of children’s bodies that determine the severity and frequency of RT infections:
• The nasal passages are narrow and short, so inhaled air is warmed less efficiently. The mucosa is swollen and rich in blood vessels, so even mild inflammation causes significant swelling. The paranasal sinuses are narrow, so inflammation persists longer.
• The lymphoid tissue of the nasopharynx, especially the adenoids, tends to hypertrophy between the ages of 2 and 7, particularly in allergic and immunocompromised children. Enlarged adenoids cause nasal obstruction and can interfere with the opening of the Eustachian tube. This disrupts ventilation of the middle ear cavity and promotes the rapid development of ear infections. Viral infections in the nasopharynx last longer and may be complicated by bacterial infections.
• The auditory (Eustachian) tube, which connects the nasopharynx with the middle ear, is horizontal, short, and wide, which makes it easier for nasal infections to spread into the ear and cause middle ear inflammation.
• The paranasal sinuses (maxillary and sphenoidal sinuses) become clinically significant after the age of 5 years, while the frontal sinuses become significant only after the age of 10 years. Therefore, sinusitis is more typical of older children. Younger children may develop ethmoidal sinus inflammation.
• The funnel-shaped larynx is the narrowest part of a child’s respiratory tract. Its mucosa is soft and richly vascularized, so inflammation leads to clinical symptoms of laryngitis, and stenosis may develop.
• The bronchi are narrow and have delicate mucosa with an extensive vascular network. Inflammation causes mucosal swelling and rapid development of bronchial obstruction.
• In children predisposed to allergies, the respiratory tract mucosa swells more easily, so obstruction develops more quickly during laryngitis or bronchitis, and the disease tends to recur more often.
An immature immune system leads to a weaker general and local immune response to infections and may be the cause of recurrent illness:
• The immune response of infants and young children is 2–3 times weaker than that of adults.
• The immune response is more often of the Th2 type, meaning that infection triggers an allergic inflammatory response and predisposes children to allergic respiratory diseases.
• Until the age of 3 months, humoral factors of local immunity (IgM, IgA, IgG) are practically absent, and they reach adult levels only at 4–6 years of age.
The child’s social environment, frequency of contact with infectious agents, and attendance in group settings [3,13,14] are also of great importance. Many children, once they start attending a group setting such as kindergarten, often begin to suffer from respiratory infections. Studies show that a child who starts attending kindergarten may become ill 12–14 times per year [1,3,9,10,11].
These children not only get sick themselves but also spread infections to their surroundings. Group settings such as kindergartens, schools, daycare centers, public gathering places such as shopping centers, and contact with older siblings are among the easiest places to become infected. Children exposed to passive smoking and infants who are not breastfed are more susceptible to infections.
If a four-year-old child attending kindergarten becomes ill with respiratory infections every month, and each illness lasts at least one week, it may seem that the child is constantly ill. Parents of such children are always concerned about their child’s immune status, but frequent illness in these cases is usually due to the physiological immaturity of the immune system rather than a true immunodeficiency.
Which Patient Needs More Thorough Examination
Frequently ill children complain of prolonged or constant runny nose, recurrent or persistent cough, worsened breathing, wheezing and shortness of breath, sputum production, fever or low-grade fever, and a general feeling of unwellness. These symptoms are characteristic of many acute and chronic respiratory diseases.
First of all, it is recommended to consider the most common cause: common viral respiratory tract infections. Usually, a viral respiratory tract infection lasts about 7–8 days, but a child may remain ill for up to 2 weeks. A healthy child may have symptoms of viral infections for up to 6 months per year. Early attendance at kindergarten increases the frequency of these infections, which may frighten young parents. However, most children with recurrent uncomplicated viral infections occurring fewer than 15 times per year should not be treated with antibiotics or undergo additional testing [1,3].
It is very important to distinguish the group of children who need further examination and pathogenetic treatment. Consultation with specialists may be necessary for children with recurrent lower respiratory tract viral and bacterial infections, suspected chronic infectious foci in the nasopharynx, and GERD [3,12]. The indications for early examination of a frequently ill child are presented in Table 1.
Table 1. Indications for early examination of a frequently ill child [3]
|
Conditions where a frequently ill child needs further examination: Aspects of medical history indicating the need for further examination of the disease: |
Children with identified conditions or symptoms requiring additional examination should be examined for many possible diseases, as listed in Table 2. About 30% of frequently ill children are diagnosed with allergy, leading to increased susceptibility to respiratory tract infections, recurrent rhinitis, rhinosinusitis, laryngitis, or obstructive bronchitis [15]. Therefore, it is first recommended to rule out or confirm those diseases that occur most frequently: infection foci in the nasopharynx, allergy, and GERD.
Table 2. Differential diagnosis of common diseases in frequently ill children suspected of having a chronic respiratory organ disease
| Upper respiratory tract diseases | Lower respiratory tract diseases |
|
• Infection focus in the nasopharynx: • Allergy: allergic rhinitis • GERD Consultation with an ENT physician is required |
• Allergy: bronchial asthma • Tuberculosis Consultation with a pediatric pulmonologist-allergist is required |
When to Suspect a Persistent Nasopharyngeal Infection
In recent years, infectious foci in the nasopharynx have become one of the most important causes of frequent illnesses in preschool-aged children. Acute, recurrent, or chronic adenoiditis, rhinosinusitis, tonsillitis, or otitis should be suspected in every child presenting with the following symptoms [4]:
• constant or recurrent runny nose;
• nasal obstruction;
• purulent secretions;
• postnasal drip;
• recurrent otitis media;
• cough, especially at night;
• snoring;
• recurrent bronchitis or pneumonia;
• good response to antibiotic treatment;
• ineffective asthma prophylactic treatment.
These children should be evaluated by an ear, nose, and throat specialist, who can also help diagnose and manage GERD, which often presents with atypical, chronic laryngopharyngeal symptoms [5]:
• choking;
• wheezing;
• throat clearing;
• a feeling of a “lump” in the throat;
• cough;
• mucorrhea (excessive nasal secretions);
• unpleasant breath odor.
It is also important to remember that adenoid hypertrophy, frequent rhinosinusitis, and ear infections may be associated with allergic inflammation of the nasal mucosa. Therefore, these children should be referred to a pediatric allergist for evaluation of possible allergic rhinitis.
After ruling out common diseases, it should be remembered that recurrent rhinosinusitis or otitis may also indicate rare but very important pediatric diseases, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and immunodeficiency states.
When to Suspect a Chronic Lower Respiratory Tract Disease
Bronchial asthma is the most common chronic lower respiratory tract (LRT) disease and should be considered whenever a child experiences episodes of wheezing, coughing, or obstructive bronchitis. Bronchial asthma is likely when:
• sensitization to inhaled or food allergens is detected;
• there is a positive family history of allergy;
• bronchial obstruction is triggered by allergens and other environmental factors, without clear signs of respiratory infection;
• bronchodilator therapy is effective;
• changes in spirometry and bronchial hyperreactivity are detected in older children.
This disease is so widely discussed that it is suspected in almost every child with cough or bronchitis. However, after a diagnosis of childhood bronchial asthma, other upper respiratory tract diseases (adenoiditis, allergic rhinitis, rhinosinusitis) and lower respiratory tract diseases (post-infectious cough, anatomical defects of the respiratory organs, foreign bodies in the respiratory tract) may also be present.
Post-infectious cough may persist after an acute respiratory tract infection. In young children who have had bronchiolitis, coughing, worsened breathing, and bronchial obstruction may persist for months or even years. Following pertussis (Bordetella pertussis) or mycoplasmal infection, paroxysmal coughing may persist for 2–6 months because of impaired mucociliary clearance and increased bronchial reactivity [2,3].
A foreign body in the respiratory tract should be suspected whenever a previously healthy child begins to experience symptoms of respiratory disease after choking. Diagnosis is complicated by the fact that the patient or relatives often deny a choking episode. In addition, food, plastic objects, and other non-radiopaque materials are not visible on chest X-ray. If there is even the slightest suspicion of a foreign body, bronchoscopy must be performed. It is important to remember that local inflammation, impaired lung function, and persistent cough may continue long after the foreign body has been removed.
Anatomical defects of the respiratory organs are most often congenital, although they may also be acquired after trauma or medical interventions. Congenital pathology, such as laryngo- or tracheomalacia, may go undetected in early life because newborns and young infants do not experience major physical strain, and symptoms may not be visible at rest. Only as the child grows or during the first respiratory infection do symptoms such as stridor, wheezing, or grunting become apparent.
Bronchial stenosis or external compression may mimic severe asthma for many years and can only be diagnosed by bronchoscopy and chest computed tomography.
Chronic suppurative lung diseases, systemic diseases, and immunodeficiencies may also present with asthma-like symptoms, affecting up to 10% of children [15]. However, in these cases, viral infections rapidly progress to bacterial pneumonia and chronic productive cough. The British Thoracic Society defines chronic cough as a cough lasting more than 8 weeks [3]. The urgency of evaluating a coughing child is determined not by the duration of nonproductive cough, but by the child’s general condition: if the child feels unwell, they must be evaluated immediately. According to a study conducted in the United Kingdom, prolonged isolated productive cough in children is rarely caused by bronchial asthma [3,20]. The most common cause of such a cough is bacterial bronchitis [3,16]. However, the authors of that study recommend examining children with prolonged productive cough for other suppurative lung diseases and other disorders [17].
Chronic Suppurative Lung Diseases in Children
Chronic suppurative lung diseases in children belong to the group of rare diseases, but they are very important because they lead to persistent lung infections, nutritional and growth disorders, and chronic respiratory failure. This group includes cystic fibrosis (CF), primary ciliary dyskinesia (PCD), idiopathic bronchiectasis, immunodeficiencies, and other rare disorders.
A chronic suppurative lung disease should be suspected in a frequently ill child when:
• there is a constant or recurrent productive cough with purulent sputum;
• severe pneumonia recurs, tends to be prolonged, and is resistant to conventional treatment;
• asymmetrical or focal changes in the lungs are detected during remission;
• atypical pathogens are identified;
• the child has poor growth.
There are many congenital and acquired immunodeficiencies that require diagnosis by experienced immunologists. However, these children often first present to pediatric pulmonologists. It is important to remember that primary congenital immunodeficiencies in children are rare (1:10,000), so immunological testing should only be considered after ruling out more common diseases. Most frequently ill children do not have immunodeficiency. If it is diagnosed, it is usually an immunoglobulin deficiency [14,15].
Immunodeficiencies are characterized by the “SPUR” description mentioned at the beginning of the article: severe, persistent, unusual, and recurrent diseases. They may be accompanied by hepatosplenomegaly, arthropathies, growth disturbances, and a family history of immunodeficiency. Not only neutropenia but also lymphopenia (<2.8 × 10⁹/l) may be a sign of severe combined immunodeficiency [3,18]. According to a study conducted in the United Kingdom, immunodeficiency was identified in 88% of newborns under 6 months of age who were investigated after the first episode of lymphopenia. The first symptoms of infection appeared in them on average within 5 weeks.
In immunodeficiency, upper respiratory tract infections recur most commonly, but children may also suffer from other conditions [3,14,15]:
• 8 or more episodes of otitis media per year;
• 2 or more severe sinus infections per year (for example, requiring intravenous antibiotic therapy);
• persistent oral or cutaneous candidiasis;
• ineffective continuous antibiotic therapy for 2 or more months;
• need for intravenous antibiotics to treat infection;
• recurrent bronchitis, pneumonia, abscesses, and bronchiectasis.
The etiology of infections largely depends on the type of immunodeficiency: encapsulated microorganisms, Pneumocystis jirovecii, and enteroviruses are characteristic of antibody deficiency. Chronic granulomatous disease may manifest with Burkholderia cepacia infections, and disseminated nontuberculous mycobacterial infections may occur as a consequence of interferon-gamma/IL-12 deficiencies.
Immunological tests (immunogram, immunoglobulins and their subclasses, vaccine response, complement tests, HIV test), chest CT scan, bronchoscopy, and bronchoalveolar lavage tests are often sufficient for diagnosing immunodeficiency. If the diagnosis remains unclear, lung biopsy is recommended.
Summary
• Early socialization of a child and attendance at daycare increase the risk of frequent respiratory illnesses.
• A well-collected medical history and adequate examination are the key to managing frequently ill children.
• It is important to rule out the most common causes of recurrent respiratory infections: common viral infections, allergies (bronchial asthma and allergic rhinitis), and GERD.
• It should not be forgotten that frequent illnesses are often related to upper respiratory tract pathology and chronic infectious foci in the nasopharynx. Therefore, a child with frequent illnesses should be evaluated by an ENT specialist.
• Attention should be paid to the child’s physical development, environmental factors, and concomitant pathology.
• If a chronic respiratory disease is suspected, the child should be referred to an experienced pediatric pulmonologist-allergist.
• Many rare chronic respiratory diseases can be diagnosed relatively easily; the most important thing is to suspect them.
• Immunodeficiency is not a common cause of recurrent respiratory infections, so the importance of immune system tests and immunostimulants should not be overestimated.
References
- Markova T., Chuvirov D. Frequently ill children. Adv Exp Med Biol. 2007;601:301–306.
- Bush A. Treatment of chronic cough in children. Pediatric Pulmonology and Allergology. 2006;9(1):3098–3112.
- Bush A. Recurrent respiratory infections. Pediatr Clin North Am. 2009;56:67–100.
- Recommendations for the diagnosis and treatment of rhinosinusitis, nasal polyps, and allergic rhinitis. Ed. S. Vaitkus. Kaunas; 2006.
- Pribuišienė R., Uloza V. Laryngopharyngeal form of gastroesophageal reflux disease. Educational book. Kaunas: KMU Publishing House; 2005.
- Carek P. J., Benich III J. J. Evaluation of the patient with chronic cough. Am Fam Physician. 2011 Oct 15;84(8):887–892.
- Lithuanian consensus on the diagnosis and treatment of cystic fibrosis. Ed. A. Valiulis. Vilnius: Vilnius University Press; 2010.
- Coren M. E. et al. Primary ciliary dyskinesia in children: age at diagnosis and symptom history. Acta Paediatr. 2002;91:667–669.
- Chang S. H., Yang Y. H., Chiang B. L. Infectious pathogens in pediatric patients with primary immunodeficiencies. J Microbiol Immunol Infect. 2006;39:503–515.
- Oksenhendler E., Gérard L., Fieschi C., DEFI Study Group, et al. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis. 2008;46:1547–1554.
- Chonmaitree T., Revai K., Grady J. J., et al. Viral upper respiratory tract infection and otitis media complication in young children. Clin Infect Dis. 2008;46:815–823.
- Ramsey C. D., Gold D. R., Litonjua A. A., et al. Respiratory illnesses in early life and asthma and atopy in childhood. J Allergy Clin Immunol. 2007;119:150–156.
- Miller R. L., Ho S. M. Environmental epigenetics and asthma: current concepts and call for studies. Am J Respir Crit Care Med. 2008;177:567–573.
- Jesenak M., Ciljakova M., Rennerova Z., et al. Recurrent respiratory infections in children: definition, diagnostic approach, treatment and prevention. In: Bronchitis. InTechOpen book chapter; 2011.08.
- Stiehm R. E. Approach to the child with recurrent infections. UpToDate. 2012.
- Marchant J. M., Masters I. B., Taylor S. M., et al. Evaluation and outcome of young children with chronic cough. Chest. 2006;129:1132–1141.
- Shields M. D., Bush A., Everard M. L., et al. British Thoracic Society guidelines: recommendations for the assessment and management of cough in children. Thorax. 2008;63(Suppl 3).
- Li A. M., Sonnappa S., Lex C., et al. Non-CF bronchiectasis: does knowing the etiology lead to changes in management? Eur Respir J. 2005;26:8–14.
- Urbonas G. Study on the frequency and reasons for antibiotic use in the treatment of colds in healthcare institutions in Kaunas County. Lithuanian General Practitioner. 2008;XII(5).
