PEDIATRICS Vol. 119 No. 3 March 2007, pp. 647 (doi:10.1542/peds.2006-2572)
LETTER TO THE EDITOR |
Pulmonary Manifestations in 
F508/R117H
Clement L. Ren, MD
Department of Pediatrics
University of Rochester
Rochester, NY 14642
To the Editor.—
O'Sullivan et al1 reported that children with the 
F508/R117H-7T genotype may have pulmonary manifestations of cystic fibrosis (CF). CF lung disease is characterized by chronic endobronchial infection and inflammation, which leads to progressive airflow obstruction.2 Here I present evidence that infants carrying this genotype can have airflow obstruction even in the absence of pulmonary symptoms.
The state of New York initiated CF newborn screening in October 2002 with a system similar to that of Massachusetts. C.K. was a term product of an uncomplicated pregnancy, labor, and delivery. His immunoreactive trypsinogen was elevated, which prompted CF transmembrane conductance regulator (CFTR) gene mutation analysis. This showed him to be a compound heterozygote for F508 and R117H. Intron analysis 28 showed 1 copy each of 7T and 9T. His initial sweat chloride level was of insufficient quantity for analysis, but a repeat test at 6 weeks of age revealed a chloride level of 40 mmol/L. Results of an oropharyngeal swab obtained at 5 months of age were positive for Pseudomonas aeruginosa. He received treatment with inhaled tobramycin (300 mg twice daily) for 4 weeks. Subsequent culture results obtained at quarterly intervals have been positive for Haemophilus influenzae and Staphylococcus aureus. The infant is now 17 months old, and he has had no radiographic, physical examination, or parent-reported signs or symptoms of lower respiratory tract disease. However, infant pulmonary-function tests performed at 15 months of age using raised-volume/rapid thoracoabdominal compression3 and body plethysmography4 showed evidence of obstructive lung disease, with a diminished forced expiratory flow at 75% of forced vital capacity of 46% predicted and an elevated functional residual capacity of 133% predicted.4,5
This patient and all the patients reported by O'Sullivan et al had sweat chloride levels outside the 95% confidence interval for normal newborns,6 which suggests that in infants with this genotype, even sweat chloride values of 20 to 30 mmol/L do not rule out the possibility of pulmonary involvement. This case demonstrates that patients with the F508/R117H-7T genotype can have airway obstruction even in the absence of demonstrable radiographic or clinical evidence of lung disease. These results support the 15 conclusions of O'Sullivan et al that patients with this genotype warrant close observation and follow-up. Infant pulmonary-function tests may be helpful in identifying airflow obstruction, which would support the diagnosis of CF in these infants.
FOOTNOTES
Statements appearing here are those of the writiers and do not represent the official position of the American Academy of Pediatrics or its Committees. Comments on any topic, including the contents of PEDIATRICS, are invited from all members of the profession; those accepted for publication will not be subject to major editorial revision but generally must be more than 400 words in length. The editors reserve the right to publish replies and may solicit responses from authors and others.
Please see www.pediatrics.org for instructions on submitting letters.
REFERENCES
1. O'Sullivan BP, Zwerdling RG, Dorkin HL, Comeau AM, Parad R. Early pulmonary manifestation of cystic fibrosis in children with the DeltaF508/R117H–7T genotype.
Pediatrics. 2006;118
:1260
–1265
2. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis.
Am J Respir Crit Care Med. 2003;168
:918
–951
3. Feher A, Castile R, Kisling J, et al. Flow limitation in normal infants: a new method for forced expiratory maneuvers from raised lung volumes.
J Appl Physiol. 1996;80
:2019
–2025
4. Castile R, Filbrun D, Flucke R, Franklin W, McCoy K. Adult-type pulmonary function tests in infants without respiratory disease. Pediatr Pulmonol. 2000;30 :215 –227[CrossRef][Web of Science][Medline]
5. Jones M, Castile R, Davis S, et al. Forced expiratory flows and volumes in infants: normative data and lung growth.
Am J Respir Crit Care Med. 2000;161
:353
–359
6. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis.
Pediatrics. 1996;97
:524
–528
PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  C Thauvin-Robinet, A Munck, F Huet, E Genin, G Bellis, E Gautier, M-P Audrezet, C Ferec, G Lalau, M D. Georges, et al. The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening J. Med. Genet., November 1, 2009; 46(11): 752 - 758. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
