Pediatric Annals

Diagnosing the Cause of Recurrent and Persistent Pneumonia in Children

Warren E Regelmann, MD

Abstract

A clear case definition is required to discuss a rational diagnostic and therapeutic approach to die child with recurrent or persistent pneumonia. In the available primary studies, pneumonia was broadly defined as cough, dyspnea, or tachypnea with physical findings of dullness to percussion, crackles, wheezes, decreased breath sounds, egophony (the transmission of higher frequency laryngeal sounds to the chest wall), or increased fremitus. These clinical signs and symptoms were usually, but not always, confirmed by abnormal lobar, segmental, subsegmentai, or bronchovascular shadows on chest radiogram. Recurrent pneumonia was defined as pneumonia that relapsed after resolution of these signs and symptoms.

Persistent pneumonia was difficult to distinguish from recurrent pneumonia. The clearing of the abnormal shadows in the chest radiogram and the complete resolution of signs and symptoms were not always documented in the referred patients. In the two most recent series, patients with both types of pneumonia were considered together. Persistent pneumonia was defined as pneumonia with the clinical course lasting longer than expected. Recurrent pneumonia was defined as a second respiratory illness occurring with densities present on chest radiogram.1·2

Most patients with adequately healing pneumonias will have gradually clearing densities on chest radiogram for 2 to 3 weeks with such viruses as respiratory syncytial virus and parainfluenza virus,3 6 to 8 weeks with pneumococcal pneumonia,4 and up to 12 months following adenovirus-21.5 Unfortunately, the etiologic diagnosis for most pneumonias in children is unknown, which makes the use of such guidelines based on etiologic agent less useful in practice. Pneumonia with persistent lobar, segmental, or diffuse shadows on chest radiogram that are unchanged or worsening over 2 or more weeks despite antimicrobic treatment for common bacterial pathogens is very suggestive of an underlying problem.6

Table

If there is sinusitis or otitis abo and the above tests are normal, further examination of the lung and mediastinum by computed tomography scan with thin cuts to diagnose bronchiectasis and interstitial lung disease should be performed. A scraping of the nasal turbinates to sample the nasal epithelium for ciliary structure and function, and measurement of the antibody response to bacterial capsular polysaccharides, such as those in the dodecavalent pneumococcal vaccine, also should be done.8 Increased titers to two or more of the pneumococcal capsular types 3, 6A, 7F, and 14 are to be expected in normal children over 2 years of age.9

The study by Adam achieved etiologic diagnosis in all of their cases using such a systematic approach (Table 3).2 Recent reviews of recurrent and persistent pneumonia10,11 describe the variety of etiologies that have been associated with individual cases of recurrent or persistent pneumonia. The reader is referred to these for help in arriving at an etiologic diagnosis in those children who remain undiagnosed after following the approach outlined above. A listing of these diseases is given in Table 4.

SUMMARY AND CONCLUSIONS

It is very important to note that safe and effective treatment of recurrent or persistent pneumonia in children is based on firmly establishing an etiologic diagnosis. Empiric treatment using repeated courses of antibiotics and hope is unlikely to yield cure or even good control of most of these processes and is likely to result in more cost to the patient's health and pocketbook.

Applied in a staged and systematic way, the diagnostic tools currently available should enable the clinician caring for children to diagnose most of their patients with recurrent or persistent pneumonia. Consultation with a pediatric pulmonologist will generally speed the process and help with difficult or confusing cases. Because effective therapy is available but differs greatly from one etiology to another, early accurate etiologic diagnosis is extremely important.…

A clear case definition is required to discuss a rational diagnostic and therapeutic approach to die child with recurrent or persistent pneumonia. In the available primary studies, pneumonia was broadly defined as cough, dyspnea, or tachypnea with physical findings of dullness to percussion, crackles, wheezes, decreased breath sounds, egophony (the transmission of higher frequency laryngeal sounds to the chest wall), or increased fremitus. These clinical signs and symptoms were usually, but not always, confirmed by abnormal lobar, segmental, subsegmentai, or bronchovascular shadows on chest radiogram. Recurrent pneumonia was defined as pneumonia that relapsed after resolution of these signs and symptoms.

Persistent pneumonia was difficult to distinguish from recurrent pneumonia. The clearing of the abnormal shadows in the chest radiogram and the complete resolution of signs and symptoms were not always documented in the referred patients. In the two most recent series, patients with both types of pneumonia were considered together. Persistent pneumonia was defined as pneumonia with the clinical course lasting longer than expected. Recurrent pneumonia was defined as a second respiratory illness occurring with densities present on chest radiogram.1·2

Most patients with adequately healing pneumonias will have gradually clearing densities on chest radiogram for 2 to 3 weeks with such viruses as respiratory syncytial virus and parainfluenza virus,3 6 to 8 weeks with pneumococcal pneumonia,4 and up to 12 months following adenovirus-21.5 Unfortunately, the etiologic diagnosis for most pneumonias in children is unknown, which makes the use of such guidelines based on etiologic agent less useful in practice. Pneumonia with persistent lobar, segmental, or diffuse shadows on chest radiogram that are unchanged or worsening over 2 or more weeks despite antimicrobic treatment for common bacterial pathogens is very suggestive of an underlying problem.6

Table

TABLE 1Demographics and Etiologic Diagnosis in Children With Recurrent or Persistent Pneumonia From the Midwestern United States*

TABLE 1

Demographics and Etiologic Diagnosis in Children With Recurrent or Persistent Pneumonia From the Midwestern United States*

RECENT STUDIES

In a series of 81 patients who were evaluated between 1976 and 1979 at a medical center in the midwestern United States, the diagnosis of persistent or recurrent pneumonia was made by the referring physician.1 Segmental or subsegmentai or broncho' vascular-associated densities were present on a chest radiogram. These had lasted longer than expected by the referring physician. Alternatively, a second lowerrespiratory tract illness occurred with chest radiographic densities. Children referred for possible cystic fibrosis or asthma were excluded.

The results of this study are summarized in Table 1. The children were generally in their preschool years; however, the range of ages was wide, from 2.5 months to 14.5 years. In these 81 patients, tlie most common associated primary etiologies were asthma in about 40%, aspiration in 10%, immune system abnormalities in 5%, repaired gross structural abnormalities of the respiratory tract and great vessels in 5%, infections in 4%, localized bronchiectasis in 1%, and respiratory muscle dysfunction in 1%. An associated etiology was not found in more than 33%.

Table

TABLE 2Epidemiology and Etiologic Diagnosis in Children With Recurrent or Persistent Pneumonia From the Middle East*

TABLE 2

Epidemiology and Etiologic Diagnosis in Children With Recurrent or Persistent Pneumonia From the Middle East*

In a more recent series from the Middle East, Adam and his coworkers applied a similar case definition of recurrent or persistent pneumonia without apparent cause to all patients admitted to King Khalid University Hospital in Riyadh from 1986 to 1989.2 After excluding those with neuromuscular disorders, malignancy, hematologic diseases, nutritional disorders, and known immune defects, 18 of 781 patients admitted with pneumonia met the case definition. As seen in Table 2, these children also were young, with a mean age of 5.7 years. Boys outnumbered girls by a ratio of 2:1. All had associated primary etiologies successfully defined, 33% had immune system abnormalities, 28% had primary structural and functional anomalies and tumors of the respiratory tract or great vessels, 22% had infections, 11% had idiopathic pulmonary fibrosis, and 6% had asthma.

A Staged Approach to Diagnosis

Three practical conclusions can be drawn from comparing these studies. First, asthma was a more frequent cause of recurrent or persistent pneumonia in the United States, bronchiectasis and chronic infections more common in Saudi Arabia. This is consistent with the observation that asthma in general is more prevalent in the industrialized world. Second, 10 years of progress in our ability to image the lung, perform bronchoscopy and lavage on infants and children, and diagnose immune system disorders appear to have improved our ability to make definitive etiologic diagnoses in cases of recurrent and persistent pneumonia. Third, both studies used a staged approach to diagnosis.

Patients initially should be evaluated for foreign body respiration, neuromuscular disorders, malignancy, hematologic diseases, nutritional disorders, and easily diagnosed immune defects. If these are not present, asthma is a likely possibility for patients born and raised in the United States. A careful history for recurrent wheezing, coughing with exercise or at night, a family history for asthma or atopy combined with prolonged inspiratory:expiratory ratio, and wheezes upon auscultation of the chest is a pattern very consistent with asthma, especially if combined with a chest film that shows only air trapping and scattered bronchovascular shadows. But this pattern also could be found in the early stages of cystic fibrosis, in microaspiration syndromes and some of the rarer but possible structural abnormalities of the airway. If clubbing is present, asthma is very unlikely.

If sputum is being produced, a smear and stain for identification of the predominant cell type can help to distinguish an allergic process with mainly eosinophils. If sputum is not being produced, and the etiology remains unclear, fiberoptic bronchoscopy with lavage and cell analysis can be diagnostic of airway lesions, infections, and the type of inflammatory cell recovered in the lavage and suggestive of chronic aspiration by a high proportion of lipid-laden macrophages or of recurrent pulmonary hemorrhage by the presence of hemosiderin-laden macrophages.

Measures of airway caliber, such as spirometry, and the change in airway caliber in response to ß2 agonists can document airway reactivity. However, improvement of 15% or more in peak expiratory flow or in forced expiratory volume in 1 second (FEV1) can be seen occasionally in patients with neutrophilic endobronchitis and allergic lung disease that is not asthma. Similarly, in patients with normal spirometry, individual patients with neutrophilic endobronchitis and allergic lung disease that is not asthma can have a greater decrease in FEV1 to methacholine or histamine inhalation than normal. As a group though, asthmatics require the least amount of methacholine or histamine to reduce their FEV1 by 20%. Spirometrie measures of airway caliber can be most useful in measuring improvement with therapy. Measurement of PaO2 or oxygen saturation by pulse oximetry is useful in assessing die severity of ventilation perfusion mismatch, the need for prompt intervention to support lung function, and the response to therapy.

Table

TABLE 3Systematic Evaluation of Children With Recurrent or Persistent Pneumonia*

TABLE 3

Systematic Evaluation of Children With Recurrent or Persistent Pneumonia*

A patient that meets the case definition for recurrent or persistent pneumonia, especially with lobar or segmental infiltrates or hilar adenopathy, should have a basic evaluation for likely etiologies other than asthma, since there is no sensitive and specific test for asthma. This evaluation should include duplicate sweat tests by the Gibson-Cooke method7 for cystic fibrosis, a barium swallow for vascular rings, duplication cysts, gastroesophageal reflux and tracheoesophageal fistulas, and an immunologic screen. This immunologic screen should include quantitative immunoglobulins, including IgE, for diagnosis of immunoglobulin deficiency, and of die hyper-IgE syndrome; delayed type hypersensitivity skin tests, including a purified protein derivative for diagnosis of anergy and of infection with Mycobacterium tuberculosis; a complete blood count differential and platelet count for neutropenia and evidence suggesting leukemia; and neutrophil chemiluminescence or nitroblue tetrazolium dye reduction for chronic granulomatous disease. The serum concentration of complement component C3 and the total hemolytic complement activity will detect the most important defects in the classic complement pathway associated with pneumonia. If warranted by place of residence or travel, antibody titers to histoplasma, blastomyces, and coccidiomyces should be obtained. Leukemia and lymphoma also must be considered and appropriate bone marrow or tissue biopsy obtained if the suspicion is high. Testing for human immunodeficiency vims (HIV) or for the presence of HIV viral proteins or DNA is indicated for the possibility of acquired immunodeficiency syndrome.

Table

TABLE 4Etiologic Possibilities Causing Recurrent and Persistent Pneumonias

TABLE 4

Etiologic Possibilities Causing Recurrent and Persistent Pneumonias

If there is sinusitis or otitis abo and the above tests are normal, further examination of the lung and mediastinum by computed tomography scan with thin cuts to diagnose bronchiectasis and interstitial lung disease should be performed. A scraping of the nasal turbinates to sample the nasal epithelium for ciliary structure and function, and measurement of the antibody response to bacterial capsular polysaccharides, such as those in the dodecavalent pneumococcal vaccine, also should be done.8 Increased titers to two or more of the pneumococcal capsular types 3, 6A, 7F, and 14 are to be expected in normal children over 2 years of age.9

The study by Adam achieved etiologic diagnosis in all of their cases using such a systematic approach (Table 3).2 Recent reviews of recurrent and persistent pneumonia10,11 describe the variety of etiologies that have been associated with individual cases of recurrent or persistent pneumonia. The reader is referred to these for help in arriving at an etiologic diagnosis in those children who remain undiagnosed after following the approach outlined above. A listing of these diseases is given in Table 4.

SUMMARY AND CONCLUSIONS

It is very important to note that safe and effective treatment of recurrent or persistent pneumonia in children is based on firmly establishing an etiologic diagnosis. Empiric treatment using repeated courses of antibiotics and hope is unlikely to yield cure or even good control of most of these processes and is likely to result in more cost to the patient's health and pocketbook.

Applied in a staged and systematic way, the diagnostic tools currently available should enable the clinician caring for children to diagnose most of their patients with recurrent or persistent pneumonia. Consultation with a pediatric pulmonologist will generally speed the process and help with difficult or confusing cases. Because effective therapy is available but differs greatly from one etiology to another, early accurate etiologic diagnosis is extremely important. The prognosis for those with asthma generally is very good.12 But, delay in diagnosis of other causes of recurrent or persistent pneumonia can lead to irreversible pulmonary structural damage that ultimately can only be treated by lung transplantation, if at all.

REFERENCES

1. Eigen H, Laughhn ]], Homrighausen J. Recurrent pneumonia in children and its relationship to bronchial hyperreactivity: Pediatrics. 1982;70:698-704.

2. Adam KA. Persistent or recurrent pneumonia in Saudi children seen at King Khalid University Hospital, Riyadh: clinical profile and some predisposing factors. Ann Trop Päediatr. 1991;11:129-135.

3. Osbom D. The radiologic appearance of viral disease of the lower respiratory tract in infants and children. AJR AmJ Roentgenol. 1978;130:29.

4. Jay S, Johanson W, Peirce A. The radiographic resolution of Streptococcus pneumoniae pneumonia. N Engl J Med. 1975;293:798-801.

5. Osbom D, White P. Radiology of epidemic adenovirus-21 infection of the lower respiratory tract in infants and young children. AJR AmJ Roentgenol. 1979;133:397400.

6. Regelmann W. Recurrent infection in the child. Postgrad Med. 1982;71:157-174.

7. Gibson L, Cooke E. Test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas using pilocarpine iontophoresis. Pediatrics. 1959;23:545-549.

8. Gaines A, Buckley R. Impaired antibody response to polysaccharides in association with functional asplenia. J Pediatr. 1989;114:89-91.

9. Giebink G1 Foker J1 Kim Y, Schiffman G. Serum antibody and opsonic responses to vaccination with pneumococcal capsular polysaccharide in normal and splenectomized children.; In/?a Dis. 1980;141:404-412.

10. Craven EM. Persistent/recurrent pneumonia in infants and children. Del Med J. 1991;63:537-546.

11. WaId ER. Recurrent pneumonia in children. AdV Pediatr Infect Dis. 1990;5:183-203.

12. Kjellman B. Prognosis and lung function in children with bronchial asthma and recurrent pneumonia. Acta Paediatr. 1972;61:197-202.

13. Urban MQ Schosser R, Spohn W, Wending WQ Robinow M. New clinical aspects of hereditary mucoepithelial dysplasia. AmJ Med Genet. 1991;39:338-341.

14· Regelmann W1 Filipovitch A. Lung involvement in the primary immunodeficiency syndromes. Seminars m Respiratory Medicine. 1992;13:190-204.

15. Quiet E, Bernaudin JF, Pinchon MC, Canet J. Immotile cilia disease with neonatal disclosure. Ultrastructural study. Presse Med. 1984;13:1607-1611.

16. Lucas T, Hayek GE Götz M, Stockinger L. Chronic dysplasia of the respiratory ciliary epithelium. Monatsschr Kmderfieiifcd. 1989;137:162-164.

17. Morais PD, Bernat GA, Ayerbe TV, Olivan DCMJ. Serous otitis and ciliary dyskinesia syndrome. Acta OtorrmoJanrigol Esp. 1991;42:393-397.

18. Siegler RL, Brewer ED Carey JC. New syndrome involving the visual, auditory, respiratory, gastrointestinal, and renal systems. AmJ Med Genet. 1992;44:461-464.

19. Smith KP, Cavett CM. Segmental bronchomalacia: successful surgical correction in an infant. J Pediatr Surg. 1985:20:240-241.

TABLE 1

Demographics and Etiologic Diagnosis in Children With Recurrent or Persistent Pneumonia From the Midwestern United States*

TABLE 2

Epidemiology and Etiologic Diagnosis in Children With Recurrent or Persistent Pneumonia From the Middle East*

TABLE 3

Systematic Evaluation of Children With Recurrent or Persistent Pneumonia*

TABLE 4

Etiologic Possibilities Causing Recurrent and Persistent Pneumonias

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