 |
|
Original Articles Indian Pediatrics 2000;37: 1085-1092 |
|||||||||
| Recurrent / Persistent Pneumonia | |||||||||
|
Recurrent or persistent pneumonia pose a significant challenge to the pediatricians. While acute lower respiratory tract infections remain the most important cause of mortality and morbidity in under fives in the developing countries, recurrent and persistent pneumonias are not uncommon. The incidence of all respiratory infections in developing countries varies from 4.2-8.7 per child per year(1,2); however, the incidence rates for pneumonia are much lower, about 10 per 100 children per year(1,2). There is no consensus on the definition of either recurrent or persistent pneumonia. Recurrent pneumonia has been defined as two episodes of pneumonia in 1 year or three episodes in any time frame(3). One has to be sure that the recurrent infections are lower respiratory tract infections before the child is investigated for recurrent pneumonia. Persistent pneumonia implies a chronic, non-resolving pneumonia. It is defined as persistence of symptoms and radiographic abnormalities for more than 1 month(3); however, some authors prefer to use the cut off of 3 months. The speed of radiographic resolution depends on the etiologic agent; this may vary from 2 weeks with respiratory syncytial virus (RSV) or parainfluenza virus infection to as long as 12 months with adenovirus infection(4-6). Therefore, it is difficult to arrive at one particular cut-off for defining persistent pneumonia. For differentiation between recurrent and persistent pneumonia, presence of a symptom free interval during which chest radiographs show clearing of infiltrates, suggests recurrent infection. At times persistent infections may present as recurrent infections because of inadequate or inappropriate therapy. The aim of the present paper is to discuss the common causes that may present as recurrent/persistent pneumonia and the approach to such a patient.
Recurrent and persistent pneumonias usually result from deficiences in the local pulmonary or systemic host defenses or from underlying disorders that modify the lung defenses(7). The causes of recurrent and persistent pneumonias overlap considerably; hence, are discussed together. The underlying disorders associated with these infections can be broadly classified into the following categories:
Table I shows the probable causes of recurrent or persistent pneumonias. Congenital malformations of the airway may predispose the child to repeated aspirations, leading to pneumonia. Congenital anomalies of the lung such as sequestration, hypoplasia, congenital adenomatoid malformation of the lung may also act as the underlying cause of recurrent or persistent pneumonia. Anomalies of the cardiovascular system especially left to right shunts increase the risk of recurrent pneumonias. Table I - Etiologic Factors for Recurrent or Persistent Pneumonia A. Congenital Malformations 1. Airways Cleft Palate Pierre Robin syndrome Tracheoesophageal fistulae Tracheomalacia 2. Lungs Pulmonary hypoplasia Pulmonary sequestration Congenital adenomatoid malformation of the lung Bronchogenic cyst 3. Cardiovascular Congenital heart disease, especially L R shunts Vascular ring B. Aspirations Gastro-esophageal reflux Swallowing abnormalities Foreign body Anomalies of the upper airways C. Defects in the clearance of airways secretions Cystic fibrosis Abnormalities of the ciliary structure of function Abnormal clearance secondary to infections, repair of congenital defects Airway compression (intrinsic/extrinsic) e.g., mediastinal tubercular lymphadenopathy D. Disorders of local/systemic immunity Primary immunodeficiencies Acquired immunodeficiencies HIV Infection Immunosuppressive therapy Malnutrition Recurrent or chronic aspiration may be associated with anomalies of the upper airway, abnormal swallowing, gastro-esophageal reflux (GER) or neuromuscular disorders. Aspirations alter the pulmonary host defenses. Defects in clearance of airway secretions may be because of abnormalities of respiratory mucus as in cystic fibrosis or defects in mucociliary function - which may be due to structural defects of cilia or secondary to various infections. Compression of the airway (intrinsic/extrinsic) interferes with the clearance of airway secretions. Various inherited and acquired disorders of immunity predispose the child to respiratory infections, in addition to infection at other sites. Occasionally, disorders of immune system may be localized just to the lungs. Severe malnutrition and deficiency of trace elements such as zinc may predispose a child to various infections; however, the exact role of these in recurrent LRTI is not well studied. Non-infectious disorders such as asthma, hypersensitivity pneumonias, pulmonary hemo-siderosis, and sickle cell disease may be responsible for recurrent or migrating lung infiltrates. Persistent lung infiltrates may also be caused by congenital anomalies such as lung cysts and sequestration, even in the absence of infection. Pulmonary hemosiderosis, hyper-sensitivity pneumonitis, sarcoidosis, interstitial pneumonitis, alveolar proteinosis, collagen vascular diseases and eosinophilic pneumonias are also associated with persistent lung in-filtrates. These conditions should be considered in a child with recurrent or persistent lung infiltrate, if infection seems unlikely. History and clinical examination may offer clues for these conditions. There is scant data available on the causes of recurrent or persistent pneumonia in children. Most of the available literature is from the west, with hardly any information from the developing countries. In a study on 184 children referred for evaluation for chronic lung disease to a teaching hospital, diagnosis related directly, or indirectly to chronic lung disease was found in 22%(8). Among the rest, bronchiectasis was seen in 9%, chronic pneumonia in 9%, chronic diseases with wheezing in 56% and no significant lower respiratory disease in 4%(8). In this study, 48% of the children actually had recurrent pneumonia. Eigen et al. could identify a definite etiology in only 20 of 81 children referred for recurrent or persistent pneumonia; 8 of these 20 had significant neuromuscular dysfunction or mental retardation or both(9). In 61 children without any apparent cause, 18% were wheezing during initial visit, 31% had a history of wheezing and 49% had a history of allergy or family history of asthma. This study suggested that asthma is a common cause of persistent or recurrent pneumonia in children and that this may occur as the initial symptom even in the absence of wheezing. Eighteen Saudi children were evaluated for etiology of persistent or recurrent pneu-monia(10). Immune and inherited metabolism disorders were found in 44.4% and anatomic abnormalities in four (22.2%). None of the children had tuberculosis, pertussis or cystic fibrosis. In a recently published study, oropharyngeal incoordination with aspiration syndrome was the commonest underlying cause in 238 children with recurrent pneumonia being identified in 48% children(11). The other important causes were immunity disorders (10%), congenital heart disease (9%), and pulmonary anomalies (8%). No underlying cause could be determined in about 8% of these children. There are no published data on etiology of persistent or recurrent pneumonia in children in India. Upadhyay et al. reported seven Indian children in United States with recurrent pneumonia and attributed the presentation to various food allergies(12). One hundred and fifty seven children were evaluated for recurrent or persistent pneumonia (excluding left to right shunts and tuberculosis) during 1996-98 in the Pediatric Chest Clinic at All India Institute of Medical Sciences, New Delhi (unpublished data). Structural abnormalities of upper and lower respiratory tracts were observed in 40 children. Forty-one children were diagnosed to have cystic fibrosis, while 21 had recurrent aspirations due to various causes. Twenty-one children were immunodeficient, of whom 17 had HIV infection. Asthma was diagnosed in 8 children. No etiology could be determined in 19 children. This pattern may not be representative as this is based on a biased sample of referred patients. Cystic fibrosis may have been over-represented because of the availability of diagnostic facilities for the same at the institute. The studies from the west have not listed cystic fibrosis as a cause possibly because it is daignosed more readily and early, and are treated separately. The paucity of data from India emphasizes the need for further studies in this area. While tuberculosis is probably the most important cause of persistent pneumonia in developing countries, it is usually diagnosed easily, given the high index of suspicion. It is likely that the causes of recurrent/non-tubercular persistent pneumonias are similar to those in the developed countries.
There are no systematic data available on the etiologic organisms responsible for recurrent and persistent pneumonia. Tuberculosis is likely to be an important cause of persistent pneumonia especially in countries like India. The common organisms responsible for acute LRTI may also be the responsible agents for recurrent infections in a child who is immunocompetent. Infections with cytomegalovirus, chlamydia may also lead to persistent infiltrates. How- ever, immunocompromised children are more likely to be infected with atypical organisms such as Pneumocystis carinii, fungi, legionella, etc.(13).
Since respiratory tract infections (mostly upper tract) are common in early childhood, it is important to be sure about the site of infection before a child is subjected to the detailed workup for recurrent pneumonia. It is important to differentiate recurrent pneumonias from episodic illnesses like asthma. Asthma may wrongly be diagnosed as bronchopneumonia and because of repeated episodes, the child may erroneously be subjected to work-up for recurrent pneumonia. This problem may be sorted out by a careful assessment of the history and physical examination. There is need to separate out the cases of just chronic cough without any features suggestive of infection of the lower respiratory tract. Often differentiation between recurrent and persistent infections may be difficult. The issue may be sorted out if sequential radiographs of the chest are available. It is also important to recognize that persistent radiographic abnormalities may be present because of atelectasis and non-infectious disorders, which have been mentioned above. Before proceed-ing to the investigations, a good history and physical examination are mandatory. There are several features that may help in reaching a diagnosis. 1. Age of onset Onset of symptoms soon after birth increase the possibility of presence of hereditary/congenital disorder. Congenital malformations such as tracheoesophageal fistula, cystic adenomatoid malformation and congenital lobar emphysema present early in life. Disorders of humoral immunity usually present in later infancy. 2. Details of the episodes A detailed account of the first episode of pneumonia and subsequent episodes should be obtained: onset, nature and duration of cough, occurrence of fever, documentation of signs of LRTI by a physician, radiographic evaluation. type and duration of antimicrobial therapy (adequte/appropriate), response to therapy and need for hospitalization. It is important to differentiate these episodes from recurrent wheezing episodes. The parents should be asked about the timing of the symptoms in relation to feedings and the change in position, vomiting, irritability, and nocturnal symptoms of coughing and wheezing. In a child with depressed cough reflex, coughing or gagging may be minimal or absent. Sleep disturbances may be seen in gastro-esophageal reflux, and obstructive lesions, especially of upper respiratory tract(14). 3. Past history/Associated complaints Occurrence of repeated infections at other sites should be asked for; a positive history may suggest systemic immunodeficiency. The type of infections may give a clue to the type of immunodeficiency. History of foreign body inhalation should be elicited. Diagnosis of tuberculosis in the past should not be ignored. Symptoms suggestive of malabsorption may be present in cystic fibrosis. 4. Perinatal history Prematurity, history of bronchopulmonary dysplasia or prolonged exposure to oxygen, maternal infections, and blood transfusions should be looked for. Occurrence of meconium ileus or delayed passage of meconium should arouse suspicion of cystic fibrosis. 5. Family history It is important to enquire about any family history of allergic disorders, asthma, cystic fibrosis, and congenital anomalies. Occurrence of recurrent infections in other family members may suggest immunologic disorder. An inquiry about the high risk behavior or history of blood transfusion in parents is essential, to rule out exposure to maternal HIV infection, in a child where immunodeficiency is suspected. 6. Environmental history Risk factors for sources of exposure to respiratory infection should be evaluated. Exposure to inhaled pollutants, irritants and passive tobacco smoking should be carefully assessed.
The aim of the physical examination is to document presence of respiratory disease, localize the site of infection, and to detect any underlying etiologic factor. General physical examination should include evaluation of growth and development, and inspection for clubbing of the fingers or toes. Clubbing may be present in chronic disorders like bronchiectasis, cystic fibrosis, and bronchiolitis obliterans. The patient should be assessed for lymphadenopathy, presence/ absence of tonsillar/adenoidal tissue. Tonsils may be absent in hypo/agammaglobulinemia. Generalized lymphadenopathy may be present in tuberculosis, HIV infection, and histiocytosis. Careful examination may reveal abnormalities of upper respiratory tract. Certain morphologic features may point towards specific disorders e.g., presence of "fish mouth" with hyperteleorism in DiGeorge’s syndrome, telangi-ectasia of eyes/ears in ataxia telangiectasia. Skin should be examined for evidence of infective foci or any rash. Respiratory system examination includes assessment of respiratory rate, evidence of distress, thoracic deformities, wheezing, stridor, the dimensions of the chest and careful auscultation of the chest to localize the infection. Evaluation of nose, paranasal sinuses and ears is mandatory. Nasal polyposis may be an important clue to cystic fibrosis. Recurrent middle ear infection may occur in immuno-deficiency syndromes and ciliary dyskinesia syndromes. As left to right shunts (anomalies of CVS) predispose to recurrent LRTI, these should always be looked for. Dextrocardia may offer a clue to immotile cilia syndrome. Chronic hypoxemia due to chronic pulmonary disorder may lead to cor pulmonale. Whenever the diagnosis of aspiration is considered, observation of the child during feeding is essential. Nasopharyngeal regurgita-tion, difficulty in sucking/swallowing, and associated coughing/choking should be looked for. The palate, tongue, and oropharynx should be inspected for any anomalies. Based on history and physical examination, the severity of the disorder can be assessed. The following features suggest a severe disorder: (i) Failure to thrive; (ii) Limitation of activity; (iii) Persistent fever; (iv) Persistent tachypnea and respiratory distress; (v) Persistent hyper-inflation; (vi) Significant/sustained hypoxemia; and (vii) Persistent radiographic/PFT abnormalities. Presence of clubbing, growth retardation, increased A-P diameter of the chest indicate chronicity of the disease/infection. It is difficult to construct an algorithm for assessment of a child with recurrent or persistent pneumonias because of the wide range of causes. It is important to consider each case individually to decide the plan of investigations accordingly.
Investigations should be planned only after careful evaluation of history and examination findings. As the causes of recurrent or persistent pneumonias are so many, the child should be investigated judiciously. It is absolutely necessary to rule out tuberculosis and underlying cardiovascular disease before proceeding to the further investigations. The diagnosis of tuberculosis may be suggested by presence of an adult with tuberculosis in the family, a positive tuberculin reaction and chest radiography. The diagnosis may be confirmed by various investigations available(15), but often the child is treated if the earlier mentioned situation is present. Radiographic evaluation of chest is essential for localization of infiltrates, their extent and resolution over time, in any child having recurrent or persistent pneumonia. Specific areas of pulmonary infiltrates should be identified on all chest radiographs, especially in children with recurrent pneumonias. Recurrence of infiltrates in same localized area is suggestive of obstruction by a foreign body or congenital anomaly or a tumor. Infiltrates which recur in different lobes/segments, are more likely to be seen in generalized disorders such as cystic fibrosis or immunodeficiencies. However, recurrence of diffuse infiltrates especially in right middle lobe, lingula or the lower lobes is suggestive of aspiration. Computed tomography of the chest, magnetic resonance imaging and broncho-graphy may be required for detailed evaluation of the lungs and the airways. Computed tomography is particularly useful in diagnosing structural anomalies such as cysts, sequestration, lobar emphysema, tumors and presence of enlarged lymph nodes. It also helps in defining the extent of involvement of the lung, especially in diseases like bronchiectasis. High resolution CT is a more advanced modality for imaging of the lungs and the airways. Pulmonary function tests, commonly performed using spirometer, are usually feasible only in children >5 years age. The major role of spirometry is to evaluate the airway hyperreactivity. If PFT are normal and still, there is strong clinical suspicion of bronchial hyper-reactivity; challenge tests (using methacholine) may be performed(9). The other purpose of performing these tests is to quantify the severity of the illness. Bronchoscopy is indicated if abnormality of bronchial anatomy or foreign body aspiration is suspected. In addtion, bronchoalveolar lavage (BAL) can be performed in at attempt to identify the etiologic agent. The BAL fluid should be subjected to microbiologic evaluation and cytopathology. Isolation of mucoid Pseudomonas aeruginosa is a strong pointer to the diagnosis of cystic fibrosis. Demonstration of Pneumocystis carinii suggests underlying immunodeficiency. For recurrent aspiration,
various studies aimed at evaluation of swallowing and gastroesophageal
reflux are indicated. Barium swallow and cine esophagogram may help in
identifying the disorders of swallowing. Radionuclide scans, esophageal
pH monitoring may be done to confirm GER. While demonstration of GER is
easy, documentation of relationship of GER to recurrent or persistent
pneumonia is difficult. Presence of lipid laden macrophages in bronchial
washings has been found to be of value in confirming recurrent or
chronic aspiration(16). Quantitation of lipid laden macrophages in bronchial washing is a better marker of aspiration (16). Radionuclide salvigram can identify chronic salivary aspiration (17). "Milk technetium acan" may demonstrate aspiration(18).
Most children reffered because of recurrent pneumonias do not have specific immunologic defect. Various minor defect have been identified in these children (20). In the present scenario, when the prevalence ofHIV infection is rapidly increasing in our country, effort should be made to look for risk factors for HIV infection, as has been mentioned earlier. A systemic immunodeficiency is suspected if in addition to recurrent pneumonisa, there is evidence of infection at other sites e.g., skin, gut, etc. The presence of other features of the recognized specific immunodeficiency syndrome provides supportive evidence for disorders of systemic immunity. The initial investigations includes complete and differential blood counts, quantitative serum immunoglobulins and skin tests of delayed hypersensitivity. Further investigations may include T and B cell subset quantification. If phagocytic defects are suspected, screening tests include neutrophil count and nitroblue tetrazolium test. Contributors: SKK and RL reviewed the literature and drafted the article. SKK will act as the guarantor for the paper. Rakesh Lodha is a Senior Research Associate of Council of Scientific and Industrial Research, New Delhi. Funding: None.
|
