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* From the Departments of Otolaryngology (Drs. Henriksson, Westrin, and Stierna), Pediatrics (Drs. Karpati and Hjelte), and Medical Nutrition (Dr. Wikström), Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
Correspondence to: Gert Henriksson, MD, Division of Otorhinolaryngology, Karolinska Institute, Huddinge University Hospital, SE-141 86 Huddinge, Sweden; e-mail: Gert.Henriksson{at}ent.hs.sll.se
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Abstract |
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Patients and study design: The clinical histories, endoscopic investigations of the nasal cavity, and analyses of nasal lavage fluid of 44 patients with CF complicated with nasal polyposis have been compared with those of 67 CF control subjects. The patients were examined at annual control examinations (with pulmonary tests, working capacity, liver tests, and bacterial and blood tests) from 1995 to 1996 at Stockholm Cystic Fibrosis Center, Huddinge University Hospital. All patients were > 2 years of age. The endoscopic findings were related to the actual pulmonary function, inflammatory blood parameters, colonizing pathogens, antibodies (Staphylococcus aureus and Pseudomonas aeruginosa), and genotype.
Results: The patients with nasal polyps differed with respect to chronic colonization of P aeruginosa in sputum samples and had a higher occurrence of serum antibodies against the same species. The two groups did not differ in pulmonary functions, inflammatory parameters, or genotype. The polyps found were mainly small (within the meatus media) and gave no significant increase in ongoing clinical symptoms such as rhinorrhea, nasal obstruction, or hyposmia. Neither was any significantly marked finding concerning the nose (mucosal swellings, secretion, etc.) made in the polyp patients. The patients with CF scored slightly lower in a smell identification test in comparison with the healthy control group. The nasal lavage fluid was analyzed (in 93 of the 111 patients) for the occurrence of P aeruginosa (by polymerase-chain reaction [PCR]), interleukin [IL]-5, IL-8, and lysozyme. The lysozyme and IL-8 content was equal in the two CF groups but increased in comparison with the healthy control group. P aeruginosa was not detected with PCR in any nasal lavage fluid. No measurable levels of IL-5 in the nasal lavage were found.
Conclusions: There was a higher frequency of chronic colonization of P aeruginosa in the lower respiratory tract in patients with nasal polyps. Otherwise, nonsevere nasal polyposis was not an indicator of lower respiratory tract morbidity in CF patients.
Key Words: cystic fibrosis • interleukin-8 • muramidase • nasal lavage fluid • nasal polyps • polymerase chain reaction • Pseudomonas aeruginosa • smell
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Introduction |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
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-F508, 394delTT, and 3659delC. The
clinical manifestations of the disease include pancreatic enzyme
deficiency with malabsorption; chronic progressive obstructive
pulmonary disease; chronic pulmonary infection with
Staphylococcus aureus, Pseudomonas aeruginosa, or
both; and an abnormal electrolyte loss in sweat. The otolaryngologic manifestations of CF include chronic sinusitis and nasal polyposis. Sinusitis based on various signs/symptoms has been reported in 11 to 94%.1 2 3 4 5 6 Radiographic signs of sinopathy (opacifications and/or liquid levels) have been shown with plain radiographs in 92 to 100%2 7 8 and with CT in 100% of the CF patients investigated.9 10 Sinonasal disease may be the source of significant morbidity in the population of patients with CF.
The prevalence of nasal polyposis has been estimated at 7 to 56%,1 2 5 6 7 10 11 12 13 14 15 with the higher prevalence when the patient was examined with an endoscopic technique. Topical nasal steroids have been administered in the case of small polyps and usually resulted in some polyp shrinkage and reduction of the associated symptoms.7 13 16 17 Larger polyps usually demand polyp surgery (which is the second most common class of operations performed on CF patients).2 Polypectomy is the simplest procedure and provides satisfactory relief of nasal obstructive symptoms, but symptomatic recurrence occurs in about 60% of patients within 18 months.2 18 A more aggressive procedure that is becoming widespread is endoscopic sinus surgery (ESS), which decreases the polyp recurrence and enhances the drainage of the paranasal sinuses. ESS has been well tolerated by CF patients and provides good symptomatic relief.19
One earlier study20
reported a correlation between nasal
polyposis that required surgery and two specific genotypes: the
-F508/-F508 and the -F508/G551D
genotypes. Another study15
showed a
genotype-phenotype correlation (-F508 homozygote) for the
paranasal sinus diseases (nasal polyposis and chronic sinusitis) in
patients with CF. The purpose of this study was to determine the
frequency of nasal polyposis in CF patients attending the Stockholm CF
Center, to relate the findings to the infectious and inflammatory
status in the nose by studying the nasal lavage fluid, and to correlate
the upper-airway findings to the total health situation of these
patients, including lower airway status, morbidity, and bacteriology,
as well as to the genotype.
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Patients
All CF patients, except those < 2 years old, attending the
Stockholm CF Center, Huddinge Hospital, were offered an examination of
their upper respiratory tract at their yearly control examination in
November 1994 to December 1996. The annual control examination at the
CF center includes pulmonary radiographs, lung function tests, working
capacity test, 
sound of the liver, inflammatory parameters
(C-reactive protein [CRP], albumin, haptoglobin, -acid
glycoprotein, erythrocyte sedimentation rate [ESR] and WBC count),
liver function tests, serum tocopherol, serum retinol, and
cultivations and antibodies for S aureus and P
aeruginosa.
The diagnosis of CF was based on repeated positive sweat test finding (> 60 mmol/L of chloride in an adequate sample of sweat). Repeated borderline measurements (40 to 60 mmol/L) were required in addition to clinical correlation or DNA genotyping for diagnosis.
The CF patients in the county of Stockholm are examined monthly; CF
patients outside the county are examined at least yearly at the center.
Bacterial samples are taken (nasopharynx or sputum) monthly. Signs of
low-grade infection (ie, increased cough, changes in sputum,
inadequate gain of weight/weight loss, lowered appetite, tiredness,
worsening of symptoms at physical examination) are indications
for antibiotic treatment. The above-mentioned signs usually
correlate well with a slight rise in inflammatory markers. The choice
of antibiotics depends on the result of the bacterial cultivation. The
length of the course of antibiotics is usually 10 days. Patients with
elevated staphylococcal antibodies ( toxin and teichoic
acid) are receiving continuous flucloxacillin treatment. Otherwise, our
center does not practice any prophylactic treatment. The patients are
regularly treated with high oral doses of mucus-dissolving agents three
times daily (bromhexin and acetylcysteine in double recommended doses).
They inhale salbutamol (usually 2.5 mL [1 mg/mL]) and acetylcysteine
(usually 2 mL [200 mg/mL]) bid or tid. Small children are recommended
nightly mist-tent therapy. The patients are supplemented with E
vitamins (100 to 400 mg/d depending on the level of -tocopherol in
blood sample) and A vitamin (5,000 to 7,500 IU/d) as well as pancreatic
enzymes in the case of pancreatic insufficiency (85% of the CF
patients).
Study Design
Clinical data on nasal symptoms were obtained by interviewing
the patients and/or their parents. After the interview, endoscopic
examination of the nasal cavity was carried out. The occurrence of
nasal polyposis, nasal congestion, secretion, redness, and the presence
of an adenoid were noted. The nasal polyps were graded according to
their size, with grade 1 equal to the smallest size of polyps
(concealed in middle meatus, not reaching the inferior edge of the
middle turbinate). Grade 2 described a polyp in the middle meatus,
reaching the inferior border of the middle turbinate. Grade 3 was equal
to a nasal polyp extending into the nasal cavity below the edge of the
middle turbinate but not below the inferior edge of the inferior
turbinate, whereas a polyp filling up the nasal cavity was regarded as
a grade 4 polyp. Nasal lavage fluid was gathered with the following
procedure: 3 mL of phosphate-buffered saline solution was poured into
the antral part of the nose by means of a syringe with a cap on top to
prevent the solution from leaking aside. The solution was poured twice
(in and out) from the syringe into the cavity while the patients were
leaning forward. The gathered solution was immediately spun at
340g by a tabletop centrifuge (Sorvall RT 6000D; Kendro
Laboratory Products; Newtown, CT) for 10 min. The supernatant
was separated from the "pellet" (equal to 1 mL of the supernatant
with some nasal secretion and nasal mucosal cells). The pellet was then
spun one more time (3,500g for 2 min) [MSE MicroCentaur;
Thistle Scientific Ltd; Uddingston, Glasgow, UK]. All
tubes were then immediately stored in a - 70°C freezer. The pellet
was analyzed for polymerase chain reaction (PCR)-detection of P
aeruginosa, immunoassays for interleukin (IL)-5 and IL-8, while
the remaining supernatant was analyzed for lysozyme content. Patients
> 14 years old evaluated their sense of smell with the Smell
Identification Test (Sensonics; Haddon Heights, NJ).
The collected data from the otolaryngologic examination were compared
with the data routinely gathered at the annual control examination at
the Stockholm CF center with regard to pulmonary function, colonization
of S aureus and P aeruginosa in sputum samples,
and other blood parameters (ESR, WBC count, proteins signaling
inflammation, total serum IgE, etc.). Chronic colonization of the
above-mentioned bacteria was defined as six consecutive isolations
separated by 
1 month for P aeruginosa and/or elevated
level of antibodies (P aeruginosa anti-exotoxin A).
The patients with polyps were offered treatment with a topical steroid (budesonide) in the form of nose spray (50 µg in both cavities bid). These patients were offered a follow-up examination 1 month later.
A sex-matched and age-matched control group consisting of 42 healthy volunteers was monitored during 1997 (20 male and 22 female subjects; mean ± SD age, 18.79 ± 10.41 years; range, 4 to 44 years). This group underwent nasal lavage and the Smell Identification Test mentioned above. In this group, no airborne allergy was allowed, or any ongoing nasal symptoms (no nasal congestion, no ongoing infection in the nasal area). No earlier surgery in the nasal or sinus region was allowed or any ongoing nasal medical treatment.
Statistical Analysis
The following statistical analyses were performed with
statistical software (Statistica; StatSoft; Tulsa, OK):
multilinear regression (age, lung function tests, some of the blood
parameters); 
2 test (genotype, sex, clinical
status, some of the operations, tendency to allergy, acute otitis media
and sinusitis, and ongoing symptoms such as snoring, rhinorrhea, mouth
breathing, nasal blockage, and epistaxis); Whitney-Mann U test (some of
the blood parameters, use of IV and oral antibiotics per year, age at
diagnosis, amounts of IL-8 and lysozyme in the lavage, smell test, and
time from diagnosis to first positive cultivation of P
aeruginosa and S aureus); Fisher’s Exact Test
(sinonasal surgery, otosalpingitis, history of hyposmia, pancreas
insufficiency and continuous per oral antibiotics); logistic regression
(earlier polypectomy, recurrent nasal blockage and secretion,
antibodies against P aeruginosa and S aureus, and
number of patients with chronic colonization with P
aeruginosa and S aureus); and log-rank test (chronic
colonization of P aeruginosa and S aureus).
Ethical Permission
The Ethics Committee of Huddinge University Hospital approved
the study. Consent from the patients or their parents was obtained
before enrollment.
Methods
Lysozyme Test
Lysozyme is a marker for serous gland secretion in the nasal
cavity but can also be released from neutrophils.21
Increased lysozyme levels indicate an inflammatory status with
stimulation of serous gland secretion, degranulation of neutrophils,
and destruction of epithelial cells. The lysozyme content of nasal
lavage was determined in a colorimetric assay slightly modified from
the assay described by Ito et al.22
Materials:
Micrococcus luteus (Micrococcus lysodeikticus) and purified lysozyme to be used as a standard were obtained from Sigma (St. Louis, MO). Remasol brilliant blue R (RBB-R) sodium salt, a reactive blue dye, was the product of ICN Pharmaceuticals (Cosa Mesa, CA).
RBB-R-Labeled M luteus :
Briefly, a solution of 200 mg of RBB-R in 20 mL distilled water was added to a suspension of 300 mg of M lysodeikticus cells in 20 mL of distilled water at 50°C with stirring. During the following 30 min, 4 g of sodium sulfate was added to the mixture in several portions. A solution of 200 mg trisodium phosphate in 2 mL of distilled water was then added, and the mixture was stirred for an additional 30 min at 50°C. The reaction mixture was centrifuged (1,200g, 10 min), and the supernatant was discarded. The pellet of the labeled cells was suspended in 20 mL of 0.05 mol/L KH2PO4-NaOH, pH 7.0 and repeatedly washed with the same buffer until the supernatant became colorless. Finally, the cells were washed with distilled water and then dried by lyophilization and stored in a - 20°C freezer until use.
Lysis of Blue M lysodeikticus by Lysozyme:
Dry blue M lysodeikticus (16 mg) was suspended in 10 mL of 0.05 mol/L KH2PO4-NaOH, pH 7.0 and centrifuged once (1,200g, 40 min). The pellet was resuspended in 10 mL of the same buffer, mixed with a vortex mixer, and divided into 240-µL portions in 96-well microplates. After preincubation at 40°C, 40 µL of sample or lysozyme standard was added to each well. The mixture was incubated at 40°C for 18 to 20 h. The reaction was stopped by the addition of 5 µL of 1 mol/L NaOH to each well. The microplate was centrifuged for 15 min at room temperature (1,500 revolutions per min, 400g). One hundred microliters of the supernatant of each well was transferred to a new 96-well microplate. The absorbance was measured at 600 nm. The resulting level of lysozyme, as determined from the standard curve, was the mean value of two separate measurements. The range of the linear interval of the standard curve was 0.102 to 0.891.
Pseudomonas PCR Test
The rapid PCR detection was performed with a set comprising one
primer pair based on 16S ribosomal RNA sequence according to a method
previously used by Karpati and Jonasson.23
The PCR was
performed on a DNA Thermal Cycler (TC 2400; Perkin-Elmer; Wellesley,
MA) using two primers selected from 16S ribosomal RNA sequences
(GenBank; National Center for Biotechnology Information; Bethesda, MD).
The oligonucleotides 5'-GTGCCTGCAGCCGCGGTAAT-3' (bases 515–534) and
5'-TGCGCCACTAAGATCTCAAG-3' (bases 841–860) amplify P
aeruginosa with high sensitivity, as previously
described.23
For P aeruginosa, the PCR detected
5 x 102 bacteria per reaction and the
sensitivity was 93% compared to culture, as reported in
the same study. Positive controls (a reference strain of P
aeruginosa) were included in each run. Fifty-seven nasal lavages
were tested, including all patients with chronic colonization with
P aeruginosa in their sputum samples. The reaction mix
consisted of 10 mM Tris-HCl (pH 8.3); 50 mM KCl; 200 µM of
deoxyadenosine triphosphate, deoxycitadine triphosphate,
deoxyguanosine triphosphate, and 300 mM of deoxyuridine
triphosphate; 3 mM of MgCl2; Ultma DNA polymerase
(Perkin-Elmer) 2.5 U; uracil-N-glycosylase (UNG) [AmpErase;
Perkin-Elmer] 1 U; 20 pm of each primer; and 10 µL of target DNA
(nasal lavage fluid or positive and negative controls prepared by
heating at 98°C and sonication for 30 min) in a total volume of 100
µL. As a first step, to prevent carryover contamination, the
reaction tubes were incubated at 50°C for 7 min to cleave
contaminating amplicons. Heating at 95°C for 10 min to denature the
UNG followed this procedure. Thereafter, 30 thermal cycles were
performed: denaturation, 1 min at 94°C; primer annealing, 1 min at
55°C; and primer extension, 2 min at 72°C. After completion of the
run, PCR products were soaked at 72°C before collection and stored at
- 20°C to prevent degradation by residual UNG activity. The
amplicons were visualized by electrophoresis (1.5% agarose gel with
0.05% ethidium bromide in 0.5 mol/L
Tris/ethylenediaminetetra-acetic acid buffer).
IL-5 and IL-8
The nasal fluid levels of IL-8 and IL-5 were measured after
homogenizing the sample with a pellet and its overlying 1 mL of the
supernatant. This method produces higher cytokine levels than assays
based on supernatants.24
Measurements were made with
commercially available sandwich enzyme immunoassays
according to the recommended protocols of the manufacturer (R&D
Systems; Abingdon, UK). Cytokine concentrations in lavage fluids were
quantified by comparison with a standard curve (acting as positive
controls) [r > 0.98 for all assays]. The specific
enzyme-linked immunosorbent assay kits used were IL-8 (sensitivity,
< 10 pg/mL; dynamic range, 32 to 2,000 pg/mL) and IL-5 (sensitivity,
< 3 pg/mL; dynamic range, 7.8 to 500 pg/mL).
Spirometry
Static and dynamic spirometric measurements were obtained from
each patient > 7 years of age. Functional residual capacity was
determined by body plethysmography. Total lung capacity and residual
volume were calculated. Vital capacity, FEV1,
FEV1 as a percentage of vital capacity, peak
respiratory flow, forced expiratory flow at 50% of FVC, and forced
expiratory flow at 25% of FVC were measured separately. All
measurements were performed using a pulmonary function laboratory
(Sensor Medics BV; Beilthaven, the Netherlands). All patients were
coached by the same technicians and were familiar with spirometric
measurements.
Biochemical Analysis
Proteins signaling inflammation (CRP, albumin, haptoglobin,
-acid glycoprotein), ESR, hemoglobin, and WBC count were measured
with routine methods.
Staphylococcal and P aeruginosa Antibody Assays
Antibodies to staphylococcal teichoic acid and -toxin and
P aeruginosa exotoxin A in serum were determined by
enzyme-linked immunosorbent assay and interpreted by routine
bacteriologic laboratory.25
26
Genotype Analysis
Genotype data were available on 41 patients with nasal polyposis
and 59 patients without polyposis described by Schaedel et
al.27
The following mutations were included:
-F508, -F508-W79R, 3659delC,
394delTT, 297–3C–A, S945 L,
L206 W, R553X, G551D,
2798 + 5G–A, Y109N, 711 + 3A–G,
D1152H, R75Q-N1088, R1162X,
W1282X, G1244, and 2183AA–G.
Smell Test
The Smell Identification Test28
was used to analyze
sense of smell. Forty different smells are presented in the form of
multiple-choice alternatives (four alternatives for each smell). The
concentrations of the different smells are well over the threshold of
identification level. As three of the smells presented in the test were
typical of American countries (pumpkin pie, root beer, and skunk) the
recommended levels for hyposmia and anosmia were lowered with three
points each (in this Swedish population).
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Forty-four of the 111 CF patients (39%) revealed nasal polyps by the endoscopic investigation. The vast majority showed polyposis of grade 1 (23%) and grade 2 (45%), ie, polyps concealed in the meatus media. Only one third of the polyps were visible outside the middle meatus of the nasal cavity. No large polyps were found. The mean age of subjects in the polyp group was 18.0 ± 8.8 years (range, 2 to 37 years; females outnumbering males by 26 to 18), compared to mean age of 16.1 ± 12.4 years (range, 2 to 57 years; males outnumbering females by 35 to 32) in the nonpolyp group. In the presented data, at least 23% of the patients with CF had undergone surgical intervention for nasal polyposis (and previous surgeries on nasal polyps were more common in the polyp group) [p < 0.0001, log regression; odds ratio, 11.0].
Chronic colonization with P aeruginosa revealed either by consecutive sputum sample or high titer against P aeruginosa anti-exotoxin A was more prevalent in the patient group with polyps (p = 0.0001, log regression; odds ratio, 5.3), clearly shown when plotting a follow-up period for 20 years (p = 0.029, log-rank test). Symptoms such as tendency to recurrent nasal blockage (46% in the polyp group vs 22% in the nonpolyp group; p = 0.015, logistic regression; odds ratio, 2.1) and nasal secretion (26% in the polyp group vs 13% in the nonpolyp group; p = 0.04, logistic regression; odds ratio, 4.5) were more prevalent in the polyp group.
Of the 111 patients, 35 patients were chronically infected with P aeruginosa and 44 with S aureus. The durations of chronic colonization of P aeruginosa were 10.7 ± 6.9 years in the polyp group and 5.8 ± 4.4 years in the nonpolyp CF group. Chronic colonization was defined by culture findings in 18 of the 20 patients in the polyp CF group, by both culture and positive assay findings in 1 patient; and by a positive assay finding in 1 patient. All nonpolyp CF patients had chronic colonization defined by culture findings.
The pulmonary status in the CF group was expressed as a percentage of
the predicted. Mean FVC was 88.0 ± 20.7% predicted, and mean
FEV1 was 77.3 ± 25.2% predicted (mean
polyp-group FEV1, 75.1 ± 24.1% predicted
[n = 42]; mean nonpolyp-group FEV1,
78.9 ± 26.1% predicted [n = 58]). The most common mutation in
the CF group was the -F508, occurring in approximately
80% (41% had -F508/-F508 and 40% had
-F508 in a combination with other genotypes).
There were no differences between the polyp and nonpolyp groups concerning the ongoing symptoms of rhinorrhea, nasal blockage, snoring, mouth breathing, epistaxis, or hyposmia. No difference regarding nasal congestion, nasal secretion, mucosal rash, or size of the adenoid was seen. Lung function capacity (FEV1 and FVC) did not differ between the groups, nor did the blood parameters (hemoglobin, blood cell counts, total IgE, ESR, CRP, albumin, haptoglobin, IgG, orosomucoid). There were no differences in atopy. There was no significant difference in the use of IV or oral antibiotics and no difference in the CF transmembrane conductance regulator genotype expression.
The Smell Identification Test revealed no difference between the two CF groups. However, in comparison with the healthy control group, CF patients with or without polyps presented a slightly reduced score (p = 0.04, Mann-Whitney U test).
The lysozyme test did not show any difference between the two CF groups. Within the polyp group, the lysozyme content in nasal lavage did not differ between the group with or without chronic colonization of pseudomonas in the lower respiratory tract. In comparison with the healthy volunteers, CF patients had significantly elevated levels of lysozyme indicating an elevated inflammatory status in the sinonasal tract (p < 0.0001, Mann-Whitney U test). The levels of IL-8 were equal in the two CF groups. Within the polyp group, the IL-8 content in nasal lavage did not differ between the group with or without chronic colonization of pseudomonas in the lower respiratory tract. We found an elevated lavage content of IL-8 in the whole CF group vs the healthy volunteers (p < 0.0001, Mann-Whitney U test). No detectable levels of IL-5 were found in the nasal lavages. P aeruginosa was not identified in the lavages with PCR technique.
Only 10 of the 44 patients with polyps attended the recommended follow-up examination after 1 month of treatment with topical steroids. Therefore, no conclusions can be made about the efficiency of this treatment. The traveling distances can partly explain the low compliance.
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Discussion |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
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In this study, we found a correlation between early chronic colonization of pseudomonades in the lower respiratory tract and nasal polyps. Three mechanisms could explain this phenomenon. A mechanism supporting the hypothesis of a sinopulmonary reflex (that could lead to the colonizing of bacteria in the lower respiratory tract), a mechanism with the spillover of bacteria, or just a mechanism based on an elevated inflammatory status in both the upper and the lower airways in a parallel manner due to the basic disease. A nasobronchial relation was postulated by Gottlieb31 in 1925 and by Sluder32 in 1919. Similarly, a more recent hypothesis33 34 35 has claimed that inflammatory mediators produced in the paranasal sinuses elicit bronchoconstriction, either by stimulating neural receptors in the nose, sinuses, or pharynx, or by dripping these mediators into the lower airway. This mechanism has been discussed in the case of asthma.36 37 The second mechanism could be spillover of colonizing bacteria from the sinus to the lower airways. As radiographs of the paranasal sinuses shows opaque areas in 90 to 100% (because of mucosal swelling and/or liquid in the paranasal sinuses)2 7 8 9 10 and as P aeruginosa and S aureus are commonly found in the case of sinusitis,17 18 the latter mechanism may be applicable. This mechanism is contradicted in a study by Drake-Lee and Morgan,38 who found no correlation between sinus washouts and corresponding sputum samples.
Recently, Raj et al39 showed an association between chronic Pseudomonas colonization (in the lower respiratory tract) and rhinitis and nasal polyposis. The main issue in this study was the development of allergy in the population with chronic colonization. The study could not point out why polyps were associated with the chronic colonization nor clarify the association between allergy and polyposis. In our study, known allergic problems in patients with polyps (21%) did not exceed known allergic problems (33%) in the nonpolyposis CF group.
Consistent with earlier studies,2 13 14 17 18 we found a relatively high risk of recurrence of polyps after simple polypectomy. In the case of small-sized polyps with only mild or intermittent symptoms from the nose and paranasal sinuses, medical treatment in the form of nasal steroids proved to be adequate and effective.16 Simple polypectomy has been widely used in the case of medium-sized to large-sized polyps and has been successful in relieving the associated symptoms, but the risk of recurrence is great. It has been stated that the ESS with an opening up of the osteomeatal area (where the ethmoidal, maxillary, and frontal sinuses enter the nasal cavity) should reduce the risk of recurrence of both polyps and sinusitis.2 18 Significant reduction of the polyposis-related and sinusitis-related symptoms has been seen after such surgery in earlier studies.18 19 40 41 It is, however, unclear at what stage this procedure is appropriate. The risk of reduced and altered growth of the sinuses and the facial skeleton (in young patients) has been debated,42 but Senior et al43 found that sinus surgery in children was safe and without significant cosmetic sequelae. It is still unclear if the intervention (ESS) improves the pulmonary status. A recent follow-up study did not show any reversibility in the progressive lung disease in CF patients after ESS.44 Radical surgery before the rare cases of lung transplantation in CF patients has been advocated.45 46 An even more effective treatment (in the cases of chronic sinusitis in CF) seems to be a combination of endoscopic surgery with serial antimicrobial lavage described by Moss and King.4
The DF508/DF508 and the DF508/G551D
genotypes have previously been shown to be significantly more common
among the CF patients with more severe polyposis (ie,
demanding surgical treatment).15
20
In our study, there
was no difference in genotype between the CF groups (with and without
polyps). This may be either an effect of the limited size of the
material studied or an effect of a different tradition of medical
treatment that could inhibit polyp development. Regular oral or IV
antibiotic treatments as soon as there is the slightest sign of an
upcoming infection will reduce the conditions that could increase the
risk of polyp growth. The regular mucolytic treatment also seems to
reduce the risk of chronic sinusitis and thereby the stimulation of the
polyp formation. We know from previous studies that the sinuses of the
CF patients quite often contain P aeruginosa and S
aureus.47
Theories of an inflammatory mechanism for
the occurrence of polyps have been stated. Observations in animal
studies have pointed out P aeruginosa as a pathogen that
gives rise to a more marked infection (increasing the risk
of polyp growth).48
Perhaps mucolytic therapy plays an
important role in reducing the polyp formation due to its
action on the viscous mucus in the sinuses? These factors may together
diminish the differences between the polyp-prone patients vs the
others.
IL-8 analyzed in the nasal lavage indicated an elevated degree of inflammation in the CF patient compared to the control subjects, but no differences were found between the two CF groups. Earlier studies have shown elevated IL-8 levels in the BAL of CF patients,49 50 while IL-8 in nasal lavage fluid did not differ compared with healthy subjects.49 IL-5 in BAL in an earlier study50 was lowered in comparison to asthmatic patients. Lysozyme analyzed in the nasal lavage indicated an elevated degree of inflammation or increased secretion in the CF patient compared to the control subjects, but no differences were found between the two CF groups. Lysozyme levels (as a marker of serous secretion) were elevated in tracheal mucosa from CF patients,51 while a certain lysozyme leakage was expected from neutrophils involved in the bronchial airway pathology due to the colonization of P aeruginosa.52 No increased levels of lysozymes have so far been reported from nasal lavages of patients with cystic fibrosis.21 Elevated levels of lysozyme have been reported in nasal lavage due to induced glandular secretion from the nose.53 At the presence of recurrent sinusitis, the baseline secretion of lysozyme was enriched while these patients had a blunted cholinergic response with decreased secretion of lysozyme.54 There were no positive PCR findings of P aeruginosa in the nasal lavage. There were, however, single findings of Pseudomonas caught with cultivation of nasopharyngeal swabs, which could indicate that the lavage technique was not relevant for catching the mentioned species. We know from earlier studies47 that a culture from the nose and nasopharynx does not reflect the species revealed in the paranasal sinuses. Furthermore, the nose could only be a transient site of the Pseudomonas species. The lack of difference between the CF groups in the markers of the nasal lavage could be explained by the limited size of the polyps and of the study. The lung function test did not show any differences between the CF groups in spite of the difference in chronic colonization of P aeruginosa. This is consistent with earlier findings that did not show reduced pulmonary function in patients with polyps.20
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Conclusion |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
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Acknowledgements |
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Footnotes |
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This study was supported by grants from the Swedish Medical Research Council (project Nos. 00749 and 09522), Draco-Tika Sweden, and the Otolaryngological Society.
Received for publication June 29, 2000. Accepted for publication August 14, 2001.
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References |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionConclusionReferences |
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and IL-8 in consecutive sputum samples from cystic fibrosis patients during antibiotic treatment. Scand J Infect Dis 32,75-79[CrossRef][ISI][Medline]
toxin in patients with cystic fibrosis. Acta Paediatrica Scand 75,139-144[ISI][Medline]
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