Endoscopic sinus surgery in cystic fibrosis: effects on pulmonary function and ideal body weight.
There is some question as to whether surgical treatment of sinus disease in patients with cystic fibrosis cystic fibrosis (sĭs`tĭk fībrō`sĭs), inherited disorder of the exocrine glands (see gland), affecting children and young people; median survival is 25 years in females and 30 years in males. improves pulmonary function or helps patients achieve their ideal body weight. To investigate this matter, we retrospectively studied 17 children with cystic fibrosis who had undergone endoscopic en·do·scope
An instrument for examining visually the interior of a bodily canal or a hollow organ such as the colon, bladder, or stomach.
en sinus surgery at the University of Kentucky College of Medicine The University of Kentucky College of Medicine is a medical school found in the University of Kentucky's Chandler Medical Center in Lexington, KY. History
The Kentucky General Assembly approved the construction of the University of Kentucky Medical Center and over a 15-year period. All patients had advanced sinus disease at the time of surgery. Although there was an overall increase in mean pulmonary function values, which peaked 1 month postoperatively, no statistically significant improvements were maintained at 6 and 12 months. Nor was there any significant change in these patients' percentage of ideal body weight.
Cystic fibrosis is the most common autosomal-recessive disease in whites, affecting approximately 1 in 3,000 individuals. (1) In cystic fibrosis, abnormal sodium and chloride transport leads to obstruction and disease in the lungs, pancreas, paranasal sinuses paranasal sinuses (par´nā´zl),
n. , and sweat glands. (2,3)
Common pulmonary findings include bronchitis, recurrent pneumonia, and parenchymal pa·ren·chy·ma
1. Anatomy The tissue characteristic of an organ, as distinguished from associated connective or supporting tissues.
2. scarring. In the paranasal sinuses, nasal polyposis polyposis /pol·yp·osis/ (pol?i-po´sis) the formation of numerous polyps.
familial polyposis , familial adenomatous polyposis and bacterial colonization of retained mucus results in chronic sinusitis chronic sinusitis Chronic sinus infection ENT Inflammation of the sinuses that empty into the nasal cavity Etiology Allergic rhinitis, nasal obstruction, deviated nasal septum, tooth abscesses, URIs . Previous studies have shown some correlation between the type and severity of sinus and pulmonary infections, and they led to the formation of a hypothesis that treatment of sinus disease might improve overall pulmonary status. (4,5) However, other studies of the relationship between sinus disease, pulmonary function, and general health in cystic fibrosis patients have yielded conflicting results. (3-7) Therefore, no consensus exists regarding the benefit of treating sinus disease in cystic fibrosis.
In this article, we describe our retrospective review retrospective review,
a posttreatment assessment of services on a case-by-case or aggregate basis after the services have been performed. of the impact that surgical treatment for chronic sinusitis and nasal polyposis had on pulmonary function and body weight in children with cystic fibrosis.
Patients and methods
We reviewed the records of all cystic fibrosis patients who underwent endoscopic sinus surgery between 1985 and 2000 at the University of Kentucky College of Medicine. The study population was limited to those patients who had undergone at least 1 year of postoperative follow-up. A total of 17 patients--12 boys and 5 girls, aged 4 to 16 years at the time of surgery (mean: 12.8)--met our inclusion criteria. Preoperative pre·op·er·a·tive
Preceding a surgical operation.
preceding an operation.
the preparation of a patient before operation. sinus disease had been staged according to the Kennedy staging system, which we used at our institution because of its simplicity and popularity. (8) All 17 patients had advanced sinus disease at the time of surgery; 14 had stage III disease and 3 had stage IV disease (figure).
In all cases, endoscopic sinus surgery involved bilateral anterior and posterior ethmoidectomy, maxillary max·il·lar·y
Of or relating to a jaw or jawbone, especially the upper one.
A maxillar; a jawbone.
adj antrostomy, and removal of sinonasal polyps Polyps
A tumor with a small flap that attaches itself to the wall of various vascular organs such as the nose, uterus and rectum. Polyps bleed easily, and if they are suspected to be cancerous they should be surgically removed. . Postoperative care included oral antibiotics, nasal saline irrigation irrigation, in agriculture, artificial watering of the land. Although used chiefly in regions with annual rainfall of less than 20 in. (51 cm), it is also used in wetter areas to grow certain crops, e.g., rice. , and endoscopic debridement Debridement Definition
Debridement is the process of removing nonliving tissue from pressure ulcers, burns, and other wounds.
Debridement speeds the healing of pressure ulcers, burns, and other wounds. in the clinic. No patient experienced any major peri- or postoperative complications.
Pulmonary function was measured by calculating the ratio of forced expiratory volume forced expiratory volume
n. Abbr. FEV
The maximum volume of air that can be expired from the lungs in a specific time interval when starting from maximum inspiration. in 1 second to forced vital capacity forced vital capacity
n. Abbr. FVC
Vital capacity measured with subject exhaling as rapidly as possible.
forced vital capacity,
n a measure of the maximum rate of exhalation. (FE[V.sub.1]/FVC, expressed as a percentage). (FE[V.sub.1] is the amount of air forcefully exhaled during the first second following a full inspiration, and FVC FVC forced vital capacity.
forced vital capacity
n See forced vital capacity.
forced vital capacity. is the total volume exhaled.) Pulmonary function was also assessed by measuring the forced expiratory flow forced expiratory flow
Abbr. FEF The flow of air from the lungs during measurement of forced vital capacity. during the middle half of the FVC (FE[F.sub.25-75%]). Sex- and age-specific percentages of ideal body weight were determined for each patient on the basis of standard pediatric pediatric /pe·di·at·ric/ (pe?de-at´rik) pertaining to the health of children.
Of or relating to pediatrics. growth charts published by the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. . Given the retrospective nature of our study, genetic screening data were not available for all patients, so we did not evaluate this parameter.
Pulmonary function and weight data were recorded prior to surgery and at 1, 6, and 12 months postoperatively. Mean values for the FE[V.sub.1]/FVC ratio, FE[F.sub.25-75%], and the percentage of ideal body weight were statistically evaluated according to analysis of variance and the Fisher's "probable least squares difference" test, for which a p value of less than 0.05 indicated statistical significance.
Overall, the results of pulmonary function testing did not indicate that there had been any significant improvement following sinus surgery. Although the mean postoperative FE[V.sub.1]/FVC and FE[F.sub.25-75%] values had been higher than their corresponding preoperative values, the differences were not statistically significant (table).
Likewise, the percentage of ideal body weight had increased slightly 1 month after surgery, but no significant long-term changes were sustained (table).
In cystic fibrosis, the ability of epithelial cells to secrete chloride ions and absorb sodium ions results in a diminished net secretion of salt. Because water normally follows sodium passively, the resulting decrease in water secretion by the exocrine glands produces very thick and dry mucus, which blocks ducts and glandular glandular /glan·du·lar/ (glan´du-ler)
1. pertaining to or of the nature of a gland.
1. drainage in the lungs. A vicious circle A Vicious Circle (1996) is a novel by Amanda Craig which dissects and satirizes contemporary British society. In particular, it describes the world of publishing -- its aspiring young authors, busy agents and opportunist literary critics. of mucus stasis and obstruction ensues, culminating in progressive tissue damage and chronic infection. (2,3)
The most common abnormalities seen on pulmonary function testing in cystic fibrosis patients are a reduction in FE[V.sub.1], a smaller reduction in FVC, and an overall reduction in the FE[V.sub.1]/FVC ratio. (9) Predicted values of FE[V.sub.1] and FVC are based on studies of normal individuals, and they vary according to the subject's age, weight, height, and sex.
The pancreatic damage caused by cystic fibrosis impairs the absorption of nutrients and makes it difficult to maintain ideal body weight. (9) Patients with pancreatic disease typically have fatty stools and do not absorb fat-soluble vitamins well. Overall, pancreatic insufficiency is a significant predictor of lower survival rates in cystic fibrosis patients. (10)
In the paranasal sinuses, thick mucus results in long-term impairment of mucociliary clearance. Bacteria, typically Pseudomonas aeruginosa, colonize col·o·nize
v. col·o·nized, col·o·niz·ing, col·o·niz·es
1. To form or establish a colony or colonies in.
2. To migrate to and settle in; occupy as a colony.
3. these thick secretions and lead to the development of chronic sinusitis. In cystic fibrosis, typical sinus symptoms include headache, nasal congestion, postnasal postnasal /post·na·sal/ (-na´z'l) posterior to the nose.
1. Located or occurring posterior to the nose or the nasal cavity.
2. drainage, and mucopurulent mucopurulent /mu·co·pu·ru·lent/ (-pur´ah-lint) containing both mucus and pus.
Containing mucus and pus. rhinorrhea. (2)
The actual mechanisms of the development of nasal polyposis in cystic fibrosis remains unclear; various researchers have proposed different theories implicating im·pli·cate
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.
2. such factors as cellular hypoxia hypoxia
Condition in which tissues are starved of oxygen. The extreme is anoxia (absence of oxygen). There are four types: hypoxemic, from low blood oxygen content (e.g., in altitude sickness); anemic, from low blood oxygen-carrying capacity (e.g. , inflammation, and ciliary ciliary /cil·i·ary/ (sil´e-e?re) pertaining to or resembling cilia; used particularly in reference to certain eye structures, as the ciliary body or muscle.
1. damage. (11) In truth, the development of nasal polyps is probably a complex nonlinear process that is affected by many factors.
Sweat gland duct cells normally absorb chloride from sweat as it is delivered to the skin surface. An impairment in chloride absorption results in higher concentrations of sodium and chloride in sweat. Measurement of the sweat chloride level is one of the most important tools in the diagnosis of cystic fibrosis. Sweat chloride concentrations greater than 60 mEq/L confirm cystic fibrosis, and levels of 40 to 60 mEq/L are suggestive of it, especially if other clinical signs point to such a diagnosis. (9) Another diagnostic tool that is often used in conjunction with the sweat chloride test is the determination of the transepithelial nasal potential difference, which is altered in patients with cystic fibrosis because of their abnormal intracellular sodium and chloride concentrations. (12)
The defective gene in cystic fibrosis--the cystic fibrosis transmembrane transmembrane /trans·mem·brane/ (trans-mem´bran) extending across a membrane, usually referring to a protein subunit that is exposed on both sides of a cell membrane.
adj. conductance regulator (CFTR)--was one of the first disease-causing genes identified by positional cloning. (9) CFTR encodes a 1,480 amino acid protein that primarily functions as a chloride channel, and it regulates a number of other channels that are involved in the transport of sodium, chloride, and adenosine adenosine /aden·o·sine/ (ah-den´o-sen) a purine nucleoside consisting of adenine and ribose; a component of RNA. It is also a cardiac depressant and vasodilator used as an antiarrhythmic and as an adjunct in myocardial perfusion imaging triphosphate triphosphate /tri·phos·phate/ (tri-fos´fat) a salt containing three phosphate radicals.
A salt or ester containing three phosphate groups. . (13) The most common CFTR mutation is [DELTA]F508, a phenylalanine phenylalanine (fĕn'əlăl`ənēn'), organic compound, one of the 22 α-amino acids commonly found in animal proteins. Only the l-stereoisomer appears in mammalian protein. deletion at position 508. Approximately 50% of affected individuals are homozygous ho·mo·zy·gous
Having the same alleles at one or more gene loci on homologous chromosome segments.
Identical genes controlling a specified inherited trait. for this mutation. The clinical course of homozygous patients appears to be slightly worse than that of patients who carry other CFTR mutations. Kingdom et al found that cystic fibrosis patients with polyps that required surgery had a higher incidence of either the [DELTA]F508/G551D or the [DELTA]F508/ [DELTA]F508 genotype. (14)
Moss and King found that 83% of cystic fibrosis patients had P aeruginosa in both sinus and respiratory cultures. (4) Shapiro et al reported similar findings in their examination of bacteria in the upper and lower respiratory tracts of cystic fibrosis patients. (5)
The correlation between chronic sinus infection and the bronchopulmonary bronchopulmonary /bron·cho·pul·mo·nary/ (-pool´mah-nar?e) pertaining to the bronchi and the lungs.
Relating to the bronchial tubes and the lungs. tree led to a hypothesis that the treatment of sinus disease might lead to a decrease in pulmonary disease; however, studies of the efficacy of sinus surgery in ameliorating the symptoms of cystic fibrosis have yielded mixed results. Moss and King compared endoscopic sinus surgery alone with endoscopic sinus surgery plus maxillary sinus irrigation with tobramycin tobramycin /to·bra·my·cin/ (to?brah-mi´sin) an aminoglycoside antibiotic derived from a complex produced by Streptomyces tenebrarius, . (4) They found that monthly maxillary sinus lavages with tobramycin reduced the need for reoperation. Among patients without polyps, 84% of the nonlavage group required further surgery, compared with only 19% of the lavage lavage /la·vage/ (lah-vahzh´)
1. the irrigation or washing out of an organ, as of the stomach or bowel.
2. to wash out, or irrigate.
n. group. Among patients with polyps, the corresponding figures were 88 and 27%.
Umetsu et al reported on 4 cystic fibrosis patients who underwent bilateral Caldwell-Luc operations. (6) They found that the frequency of hospital admissions after surgery was reduced in comparison with the patients' preoperative frequency of admission. They also found that these patients experienced subjective improvements in terms of nasal obstruction and headache.
A retrospective study by Triglia and Nicollas of nasal polyps in children included 27 cystic fibrosis patients. (7) Although the authors found that the cystic fibrosis patients experienced a decrease in the need for intravenous antibiotic treatment following sinus surgery, there was little improvement in pulmonary function.
Madonna et al retrospectively reviewed the cases of 14 cystic fibrosis patients, aged 5 to 24 years, who had undergone endoscopic sinus surgery. (3) Preoperatively, all had complaints of recurrent sinusitis sinusitis
Inflammation of the sinuses. Acute sinusitis, usually due to infections such as the common cold, causes localized pain and tenderness, nasal obstruction and discharge, and malaise. and nasal obstruction, and polyps were present in 11. The authors found no statistically significant differences in preoperative, 3-week postoperative, and 6-month postoperative FE[V.sub.1], FVC, and FE[V.sub.1]/FVC values. In contrast, Halvorson et al examined the results of sinus surgery in a series of adults with cystic fibrosis. (15) Their preliminary findings indicated that endoscopic sinus surgery did improve overall sinusitis symptoms and increase exercise tolerance.
Our findings that pulmonary function in cystic fibrosis patients with sinus disease did not significantly improve following endoscopic sinus surgery are consistent with those of Madonna et al (3) and Triglia and Nicollas. (7) Although one would expect that treatment of chronic sinus infection and postnasal drainage would lead to decreased infection and inflammation of the lower respiratory tract, the failure of sinus surgery to have a significant impact on pulmonary function indicates that pulmonary function is primarily dependent on intrinsic bronchopulmonary disease. In addition, the percentage of ideal body weight, another parameter of overall health and nutritional status, did not significantly change after sinus surgery. This finding was not unexpected, however, because body weight in patients with cystic fibrosis is influenced by both pulmonary status and the degree of pancreatic insufficiency, neither of which is affected by sinus surgery.
Another treatment that has been shown to be effective in the treatment of sinus disease in cystic fibrosis is serial tobramycin irrigation of the sinuses. Moss and King concluded that postoperative tobramycin irrigations decreased the recurrence rate and the need for additional sinus surgery in their cystic fibrosis population. (4) Since tobramycin irrigations are being administered more often as part of postoperative care after endoscopic sinus surgery in cystic fibrosis patients, it would be worthwhile to examine the results of sinus surgery plus tobramycin irrigations on pulmonary function. We are currently administering routine tobramycin irrigations after sinus surgery to determine if they do indeed alter the long-term effectiveness of endoscopic sinus surgery in our patient population.
Genetic screening for CFTR mutations is commonly performed as part of the diagnostic evaluation of patients who have suspected cystic fibrosis. Because certain mutations are associated with more severe forms of sinusitis, future studies may determine that different CFTR mutations influence the response to sinus surgery.
In conclusion, endoscopic sinus surgery is safe and effective for treating chronic sinusitis and nasal polyps in cystic fibrosis patients, but our data do not support the hypothesis that it has a positive effect on pulmonary function and body weight in and of itself. We plan to conduct studies to evaluate the role of tobramycin irrigations in postoperative care and to determine whether the response to endoscopic sinus surgery is dependent on specific CFTR mutations.
Table. Pulmonary function and body weight data FE[V.sub.1]/ Pct. of ideal FVC (%) FE[F.sub.25-57%] body weight Preoperatively 59.7 43.5 83.9 1 mo postop 72.8 58.9 86.5 6 mo postop 66.6 50.7 83.6 12 mo postop 69.1 48.9 84.9 ANOVA (p value) 0.6806 0.7914 0.7993 Fisher's PLSD (p value) 0.2476 to 0.3160 to 0.5058 to 0.8309 0.9072 0.7589 None of the differences in pulmonary function and body weight data according to the various measurement parameters was statistically significant. Key: FE[V.sup.1] = forced expiratory volume in 1 second; FVC = forced vital capacity; FE[F.sub.25-75%] = maximal midexpiratory flow rate; ANOVA = analysis of variance; PLSD = probable least squares difference.
(1.) Kosorok MR, Wei WH, Farrell PM. The incidence of cystic fibrosis. Stat Med 1996;15:449-62.
(2.) Batsakis JG, El-Naggar AK. Cystic fibrosis and the sinonasal tract. Ann Otol Rhinol Laryngol 1996;105:329-30.
(3.) Madonna D, Isaacson G, Rosenfeld RM, Panitch H. Effect of sinus surgery on pulmonary function in patients with cystic fibrosis. Laryngoscope 1997;107:328-31.
(4.) Moss RB, King VV. Management of sinusitis in cystic fibrosis by endoscopic surgery and serial antimicrobial lavage. Reduction in recurrence requiring surgery. Arch Otolaryngol Head Neck Surg 1995;121:566-72.
(5.) Shapiro ED, Milmoe GJ, Wald ER, et al. Bacteriology bacteriology
Study of bacteria. Modern understanding of bacterial forms dates from Ferdinand Cohn's classifications. Other researchers, such as Louis Pasteur, established the connection between bacteria and fermentation and disease. of the maxillary sinuses in patients with cystic fibrosis. J Infect Dis 1982;146:589-93.
(6.) Umetsu DT, Moss RB, King VV, Lewiston NJ. Sinus disease in patients with severe cystic fibrosis: Relation to pulmonary exacerbation. Lancet 1990;335:1077-8.
(7.) Triglia JM, Nicollas R. Nasal and sinus polyposis in children. Laryngoscope 1997;107:963-6.
(8.) Kennedy DW. Prognostic factors, outcomes and staging in ethmoid sinus surgery. Laryngoscope 1992;102(Suppl 57):1-18.
(9.) Boat TF. Cystic fibrosis. In: Behrman RE, Kliegman RM, Arvin AM, Nelson WE, eds. Nelson Textbook of Pediatrics. Philadelphia: W.B. Saunders, 1996.
(10.) Rosenstein BJ, Zeitlin PL. Prognosis in cystic fibrosis. Curr Opin Pulm Med 1995;1:444-9.
(11.) Gysin C, Alothman GA, Papsin BC. Sinonasal disease in cystic fibrosis: Clinical characteristics, diagnosis, and management. Pediatr Pulmonol 2000;30:481-9.
(12.) Knowles MR, Paradiso AM, Boucher RC. In vivo nasal potential difference: Techniques and protocols for assessing efficacy of gene transfer in cystic fibrosis. Hum Gene Ther 1995;6:445-55.
(13.) Devidas S, Guggino WB. CFTR: Domains, structure, and function. J Bioenerg Biomembr 1997;29:443-51.
(14.) Kingdom TT, Lee KC, FitzSimmons SC, Cropp GJ. Clinical characteristics and genotype analysis of patients with cystic fibrosis and nasal polyposis requiring surgery. Arch Otolaryngol Head Neck Surg 1996;122:1209-13.
(15.) Halvorson DJ, Dupree JR, Porubsky ES. Management of chronic sinusitis in the adult cystic fibrosis patient. Ann Otol Rhinol Laryngol 1998; 107:946-52.
From the Division of Otolaryngology--Head and Neck Surgery, Department of Surgery, University of Kentucky College of Medicine, Lexington.
Reprint requests: Jose M. Manaligod, MD, Department of Otolaryngology--Head and Neck Surgery, University of Iowa Not to be confused with Iowa State University.
The first faculty offered instruction at the University in March 1855 to students in the Old Mechanics Building, situated where Seashore Hall is now. In September 1855, the student body numbered 124, of which, 41 were women. Hospital and Clinics, 200 Hawkins Dr., Iowa City, IA 52246. Phone: (319) 384-5837; fax: (319) 356-4547; e-mail: firstname.lastname@example.org