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Bacterial Pattern in Chronic Sinusitis and Cystic Fibrosis

Jose M. Godoy, Andres N. Godoy, Gloria Ribalta and Isabel Largo
Otolaryngology -- Head and Neck Surgery 2011 145: 673 originally published online 26 April 2011
DOI: 10.1177/0194599811407279

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407279
oy et alOtolaryngologyHead and Neck Surgery
The Author(s) 2010
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Original ResearchSinonasal Disorders
Bacterial Pattern in Chronic Sinusitis and
Cystic Fibrosis
Jose M. Godoy, MD1, Andres N. Godoy, MD2,
Gloria Ribalta, MD3, and Isabel Largo, MD4
No sponsorships or competing interests have been disclosed for this article.
Abstract
C
Objective. To assess the association between pathogenic bac-
teria found in bronchoalveolar lavages and paranasal cavity
cultures in patients with cystic fibrosis (CF) who underwent
endonasal endoscopic sinus surgery. The authors hypothesized
that the pathogenic bacterial pattern of the upper airway
would be associated with that of the lower airway.
Study Design. Prospective case series with planned data col-
lection.
Setting. Tertiary referral center.
Subjects and Methods. A group of 16 patients with diagnosis of
CF who underwent endonasal endoscopic sinus surgery from
July 2001 to August 2009 participated in the study. Culture
samples were obtained from bronchoalveolar lavages and
paranasal cavities. A Fisher exact test was performed to
examine the significance of the association between upper
airway and lower airway cultures.
Results. The most frequent microorganisms in cultures of para-
nasal cavities and bronchoalveolar lavages were Pseudomonas
aeruginosa, Staphylococcus aureus, and Streptococcus viridans. Statis-
tical analysis revealed a significant association between upper air-
way cultures (paranasal cavities) and lower airway cavities (bron-
choalveolar lavages) for the 2 most frequent microorganisms,
P aeruginosa and S aureus (P = .007 and P = .030, respectively).
Conclusion. The authors confirmed their initial hypothesis that
a significant association between bronchoalveolar lavages and
sinus cultures was established, once more confirming the idea
of a unified airway.They found chronic rhinosinusitis with pol-
yps to be a common clinical presentation in patients with CF.
Further studies are required to indicate the role of antibiotics
and the pathogenesis of the microorganisms as a manifesta-
tion of clinical severity.
Keywords
chronic sinusitis, endoscopic sinus surgery, cystic fibrosis,
bacteriology
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Otolaryngology
Head and Neck Surgery
145(4) 673676
American Academy of
OtolaryngologyHead and Neck
Surgery Foundation 2011
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DOI: 10.1177/0194599811407279
http://otojournal.org
Received September 9, 2010; revised March 15, 2011; accepted March
25, 2011.
ystic fibrosis (CF) is the most common fatal autosomal
recessive disease. It is a variable presenting disorder
that affects multiple systems, with an incidence of
1:3000 in the Caucasian population.1 It is caused by a muta-
tion in the transmembrane regulator gene cystic fibrosis trans-
membrane conductance regulator (CFTR), a protein forming a
complex chloride channel that is involved in various regula-
tory mechanisms. With advanced new screening techniques in
newborns, prevalence estimates are likely to rise also with the
increasing recognition of individuals with mild disease.
Mutations caused in the CFTR protein lead to a deranged
transport of chloride and other CFRT-affected ions, such as
sodium and bicarbonate, causing thick and viscous secretions
in lungs, pancreas, liver, intestine, and the reproductive tract.
Patients with CF, over a variable time course, develop chronic
airway obstruction due to thick secretions, soon followed by a
chronic colonization state,2 which leads to respiratory tract
infections. The bacterial flora that colonize the respiratory
tract include Haemophilus influenzae, Staphylococcus aureus,
and Pseudomonas aeruginosa. The latter often is present in
early childhood as a nonmucoid strain, which later on devel-
ops into a mucoid strain, causing accelerated functional pul-
monary decline.3
1
Department of OtolaryngologyHead and Neck Surgery,Vanderbilt
University, Nashville, Tennessee, USA
2
Department of OtolaryngologyHead and Neck Surgery, Johns Hopkins
University, Baltimore, Maryland, USA
3
Department of OtolaryngologyHead and Neck Surgery, Clinica Las
Condes, Santiago Chile
4
Department of Pediatrics, Medicine Faculty, University of Chile, Santiago,
Chile
This article was presented at the 2010 AAO-HNSF Annual Meeting & OTO
EXPO; September 26-29, 2010; Boston, Massachusetts.
Corresponding Author:
Jose M. Godoy, MD, Department of OtolaryngologyHead and Neck
Surgery,Vanderbilt University, 2220 Pierce Ave, Nashville, TN 37232
Email: jose.m.godoy@vanderbilt.edu
674 OtolaryngologyHead and Neck Surgery 145(4)
There is a high incidence of involvement of the paranasal
sinuses in individuals with CF, with a more than 90% inci-
dence described in the pediatric population.4 Chronic inflam-
mation of the respiratory airway epithelium, especially
paranasal sinuses, secondary to bacterial infection, results in
goblet cell hyperplasia, squamous cell metaplasia, and loss of
ciliated cells.5 These factors contribute to the obstruction of
the sinuses, resulting in stasis of the mucus and reinfection.
All of this leads, in turn, to entrapped secretions, with impaired
gas exchange between the sinuses and the bloodstream, pro-
ducing chronic infection. In addition, there is a high preva-
lence of sinus polyps involved in these patients, developing
between ages 5 and 20 years.5
Several recent studies have focused on associating geno-
types with clinical severity using computed tomography and
microbiology cultures. However, few studies have explored
the association between pathologic bacteria cultures found in
paranasal sinuses and bronchoalveolar lavages in patients
with CF. Recent studies evaluating colonization in paranasal
sinuses and lower airways demonstrate mixed flora of Gram-
positive aerobic bacteria and anaerobic bacteria, correlated
with neutrophilic inflammation.6
Colonization of the sinuses contains a distinct array of bac-
teria, with the most common being P aeruginosa, H influen-
zae, and Streptococcus.7 New insights in colonization of upper
airway and lower airway strains could play a role as a reser-
voir of S aureus and P aeruginosa in CF.8 The main objective
of the current study is to assess the association between patho-
genic bacteria found in bronchoalveolar lavages and paranasal
cavity cultures in patients with CF who underwent endonasal
endoscopic sinus surgery.
Materials and Methods
Institutional review board approval was received for this
study from Clinica Las Condes. Data collection occurred
from July 2001 to August 2009. A group of 16 patients with a
diagnosis of CF (69% male and 31% female) and a mean age
of 22.8 years who underwent endonasal endoscopic sinus
surgery participated in the study. Three patients had been
transplanted. Cultures samples from bronchoalveolar lavages
and paranasal cavities were obtained.
Procedure
In all patients, CF was diagnosed with a chloride test, and
genetic testing was carried out to determine CFTR gene muta-
tion. The tests were performed at the TAAG Laboratory.
CFTR full gene sequence analysis was performed by modi-
fied temporal temperature gradient electrophoresis.
Cultures from paranasal cavities were obtained in the oper-
ating room while the patient underwent endonasal sinus sur-
gery through direct aspiration, using the same procedure for
all subjects. The material was taken from maxillary sinus, eth-
moid sinus, or frontal sinus. Aerobic, anaerobic, and tubercu-
losis cultures were processed immediately at Clinica Las
Condes laboratory. The cultures were performed before the
patients started the antibiotic treatment. As for bronchoalveo-
lar lavages, they were done in the same general anesthetic
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procedure and were taken from the main stem bronchus and
smaller bronchi, also through direct aspiration, and cultured in
the same laboratory. Analysis included aerobic, anaerobic, and
tuberculosis study. Anaerobic samples were collected directly
on an anaerobic culture plate. Samples were cultured directly
onto a chocolate agar plate using a quantitative processing
method in agar trypticase soy with lamb blood at 5% plate
(bioMrieux, Marcy lEtoile, France), chocolate agar (BM),
and McConkey agar (BM). These plates were incubated in
anaerobiosis (except plates with agar chocolate, which were
incubated at atmospheric CO2 5% at 35C for 48 hours). The
McConkey plate was isolated for 5 days, and then the nonfer-
menting bacillus of slower growth was observed. For fungi,
they were isolated in an agar Sabouraud-dextrose plate, with
anaerobes isolated through 2 processes: SNVS and SCS, both
from bioMrieux.
Data Analysis
Data were maintained in an Excel spreadsheet. Statistical
analysis was processed in Stata 11 SE (Stata Corporation,
College Station, Texas). First, rhinosinusitis classification
was divided into polyps and without polyps according to the
clinical presentation. The classification of rhinosinusitis
established by the international meeting on Rhinitis Diagnosis
and Treatment in 1994 was applied. Because the data were
ordinal, the nonparametric Fisher exact test was performed to
examine the significance of the association between upper
airway cultures and lower airway cultures within the 3 most
prevalent microorganisms. For each culture, bacterial sensi-
tivity and resistance were also determined and tabulated. We
proceeded by generating 2 variables based on the location of
cultures: upper and lower airway. When the same microorgan-
ism was cultured in the upper and lower airway, the sensitivi-
ties and resistances were noted in parallel for each of these 2
location variables. Because of the binary nature of the data
(sensitivity 0, resistance 1), we followed with a tetrachoric
correlations analysis.
Results
Of our 16 patients, all presented chronic rhinosinusitis and
71% had polyps. The most common mutation was F508/
M470, correlating with international studies (Table 1). The
mean diagnostic age was 7.9 years.
The most frequent microorganisms in cultures of paranasal
cavities and bronchoalveolar lavages were P aeruginosa,
S aureus, and Streptococcus viridans. In the cultures of the
paranasal cavity, P aeruginosa and S aureus were the most
prevalent microorganisms, with 57% and 46% prevalence,
respectively. As for the cultures from bronchoalveolar lavages,
both P aeruginosa and S viridans were present in 46% of the
cases (Table 2).
Statistical analysis revealed a significant association
between upper airway cultures (paranasal cavities) and lower
airway cultures (bronchoalveolar lavages) for the 2 most fre-
quent microorganisms, P aeruginosa and S aureus (P = .007
and P = .030, respectively). No association was found with
S viridans between upper and lower airway cultures (P = .522).
Godoy et al 675

Table 1. Cystic Fibrosis (CF) Mutations and Variants of CF Our analysis of upper and lower airway bacteriology
Transmembrane Conductance Regulator in Patients with Chronic revealed a significant association between cultures obtained
Rhinosinusitis (CRS) from paranasal cavities and bronchoalveolar lavages for
CRS with CRS without P aeruginosa and S aureus in patients with CF who had previ-
CF Mutation Polyps (n = 8) Polyps (n = 3) ous endonasal sinus surgery. This association does not imply
causation.
F508/+ 57 0 Recent evidence suggests that upper and lower airway
M570V 0 67 colonization is polymicrobial and is associated with
R334W/T3515 M470V 0 33 increased endobronchial inflammation and poorer clinical
L9997F/F834L/7T/9T 0 33
status.11 This simultaneous colonization could be related to
M470Y/M470V 0 33
age.12 The mentioned study compared sinus and lower air-
G542X/1078 delT 17 0
way cultures in patients with CF and found that as patients
F508/P.R1066<C3328C>T 13 0
age, they are more likely to have colonization in both upper
and lower airways, starting in the sinuses at a lower age.12
This perspective highlights the association between the
Table 2. Microorganisms in Cultures from Upper and Lower maturity of the immune system in terms of age and its
Airways dynamic relation in modulating infection. In terms of the use
of antibiotics in these patients, further analysis should be
Upper Airway Lower Airway P Value
Bacteria Cultures Cultures <.05
made estimating minimum inhibitory concentration for bac-
terial isolates. In addition, we encourage performing genetic
S aureus 46 23 .030 strain correlations between the upper and lower airway in
Pseudomonas 57 46 .007 these types of patients.
S viridans 23 46 .522 Yildrim et al13 analyzed bacteriology in patients with
a
S pneumoniae 4 0 chronic sinusitis who have been medically and surgically
a
Moraxella 4 0 treated with a possible role of coagulase negative Staphylococcus
a
Haemophilus 8 4 as a pathogen involved in the chronic sinusitis process. The
a
Aspergillus niger 0 4 authors described a high incidence of positive cultures for
a
Aspergillus fumigatus 4 12
a S aureus from the sinuses of patients with chronic sinusitis
Achromobacter 0 4
after surgery, but they mention an uncertain role in the patho-
xylosoxidans
Scedosporium 0 4 a genesis or clinical course of the disease as well as its uncertain
apiospermum association with patients with CF.14
a
Corynebacterium 4 8
Candida albicans 0 8 a Conclusion
a
P value = 1.00.
Further studies are required to further comprehend the role and
impact of antibiotics and the pathogenesis of the microorganisms
as a manifestation of clinical severity. We found chronic rhino-
sinusitis with polyps to be a common clinical presentation in
As for bacterial sensitivity and resistance, when the same
patients with CF. Also, we were able to confirm our initial
microorganism was cultivated in both the upper and lower air-
hypothesis: we obtained an association between bronchoalveolar
way, the correlation pattern between these 2 locations revealed
lavages and sinus cultures, within a polymicrobial clinical set-
a perfect correlation (tetrachoric rho = 1.0, 2-sided exact P =
ting, once more confirming the idea of a unified airway. This has
.0000).
significant importance in lung-transplanted patients, in whom the
new lung may become infected from the paranasal cavities, driv-
Discussion
ing to an obliterative bronchiolitis.
Consistent with earlier studies,7 our findings confirm P aeru-
ginosa and S aureus as the most frequent bacterial organisms. Author Contributions
Muhlebach et al,9 who studied lower airway and throat cul- Jose M. Godoy, corresponding author, conception, design, acquisi-
tures as predictive values of sinus bacteriology in CF, found tion of data and interpretation, final approval; Andres N. Godoy,
that P aeruginosa and S aureus were involved as the most interpretation of data, critical revision, final approval; Gloria
frequent bacterial species. Ribalta, conception and design, drafting and critical revision of
However, few studies have specifically explored the asso- article; Isabel Largo, conception and design, drafting and critical
ciation between upper airway and lower airway chronic infec- revision of article.
tion in patients with CF who have undergone endonasal sinus
Disclosures
surgery. This could be related to the presence of sinus polyps.
Some authors describe a higher frequency of P aeruginosa Competing interests: None.
colonization in the lower respiratory tract in patients with Sponsorships: None.
nasal polyps.10 Funding source: None.
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676 OtolaryngologyHead and Neck Surgery 145(4)
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