Endoscopic sinus surgery in cystic fibrosis: effects on pulmonary function and ideal body weight.

Abstract

There is some question as to whether surgical treatment of sinus disease in patients with cystic fibrosis 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 sinus surgery at the University of Kentucky College of Medicine 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.

Introduction

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, and sweat glands. (2,3)

Common pulmonary findings include bronchitis, recurrent pneumonia, and parenchymal scarring. In the paranasal sinuses, nasal polyposis and bacterial colonization of retained mucus results in chronic sinusitis. 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 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 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).

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In all cases, endoscopic sinus surgery involved bilateral anterior and posterior ethmoidectomy, maxillary antrostomy, and removal of sinonasal polyps. Postoperative care included oral antibiotics, nasal saline irrigation, and endoscopic debridement in the clinic. No patient experienced any major peri- or postoperative complications.

Pulmonary function was measured by calculating the ratio of forced expiratory volume in 1 second to forced vital capacity (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 is the total volume exhaled.) Pulmonary function was also assessed by measuring the forced expiratory flow 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 growth charts published by the Centers for Disease Control and Prevention. 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.

Results

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).

Discussion

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 drainage in the lungs. A vicious circle 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 these thick secretions and lead to the development of chronic sinusitis. In cystic fibrosis, typical sinus symptoms include headache, nasal congestion, postnasal drainage, and mucopurulent rhinorrhea. (2)

The actual mechanisms of the development of nasal polyposis in cystic fibrosis remains unclear; various researchers have proposed different theories implicating such factors as cellular hypoxia, inflammation, and ciliary 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 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 triphosphate. (13) The most common CFTR mutation is [DELTA]F508, a phenylalanine deletion at position 508. Approximately 50% of affected individuals are homozygous 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 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. (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 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 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.

References

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(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.

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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 Hospital and Clinics, 200 Hawkins Dr., Iowa City, IA 52246. Phone: [phone]; fax: [phone]; e-mail: [e-mail]