Original articles
Surfactant protein deficiency in familial interstitial lung disease,☆☆

https://doi.org/10.1067/mpd.2001.114545Get rights and content

Abstract

Objective: To determine the contribution of surfactant protein abnormalities to the development of chronic lung injury in a familial form of interstitial lung disease. Study design: An 11-year-old girl, her sister, and their mother who were diagnosed with chronic interstitial lung disease underwent laboratory investigation of surfactant protein expression in bronchoalveolar lavage fluid and lung biopsy specimens. Nineteen patients with idiopathic pulmonary fibrosis and 9 patients who were investigated for pulmonary malignancy but who did not have interstitial lung disease served as control subjects. Results: The 3 family members were found to have absent surfactant protein C (SP-C) and decreased levels of SP-A and SP-B in bronchoalveolar lavage fluid (BALF). Immunostaining for pulmonary surfactant proteins in lung biopsy specimens obtained from both children demonstrated a marked decrease of pro-SP-C in the alveolar epithelial cells but strong staining for pro-SP-B, SP-B, SP-A, and SP-D. No deviations from published surfactant protein B or C coding sequences were identified by DNA sequence analysis. All control subjects had a detectable level of SP-C in the BALF. Conclusion: The apparent absence of SP-C and a decrease in the levels of SP-A and SP-B are associated with familial interstitial lung disease. (J Pediatr 2001;139:85-92)

Section snippets

Case histories

Patient I, an 11-year-old girl, was given a diagnosis of ILD at the age of 7 years. Her family reported that for several years she seemed to tire easily with exertion. There was no history of cough, chest pain, fever, or recurrent sinopulmonary infections. There was also no evidence of cardiac, dermatologic, gastrointestinal, hepatic, immunologic, renal, or skeletal disorders. The patient was born 5 weeks prematurely, weighing 2250 g, to a 20-year-old mother. She remained in the hospital for 3

Radiologic studies

Chest radiographs demonstrated hyperinflation in all 3 patients. HRCT showed extensive areas of decreased attenuation. Expiratory images in patients I and III showed air trapping in these areas. This appearance reflects destructive changes in the parenchyma. The presence of hyperinflation and air trapping suggests that the predominant abnormality is emphysema or cystic lung disease. Ground-glass opacity was a predominant feature in patient III. Ground-glass opacity is a nonspecific finding but

Discussion

Surfactant deficiency is the principal cause of respiratory distress syndrome seen in infants born prematurely. A selective deficiency of SP-B has also been recognized as a cause of RDS in term infants.18 Successful trials of exogenous surfactant administration in the treatment of neonatal and adult forms of RDS demonstrate that surfactant deficiency and/or abnormality of its biophysical functions play an essential role in the development of acute lung injury.19 SP-C associates with surfactant

Acknowledgements

We thank Sherri A. Profitt for her technical assistance in performing the immunohistochemistry.

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  • Cited by (0)

    Supported by grants HL-56387, HL-54703, and HL-54187 from the National Institutes of Health and the Cystic Fibrosis Foundation.

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    Reprint requests: Raouf Amin, MD, Children’s Hospital Medical Center, Division of Pulmonary Medicine, 3333 Burnet Ave, Cincinnati, OH 45229-3039.

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