6. VI MODELO DE NEGOCIO
6.7. ANÁLISIS ECONÓNICO Y FINANCIERO
6.7.1. PLAN FINANCIERO
CRSsNP are combined in this analysis.
Laryngopharyngeal reflux (LPR) is theorized to con- tribute to the pathophysiology of CRS in 3 possible ways: direct gastric acid exposure to the nasal cavity and paranasal sinuses causing mucosal inflammation and im-
paired MCC408; a vagal-mediated response in the nasal
mucosa from esophageal stimulation409; andHelicobacter
pyloriinfection.410
Ulualp et al.411 demonstrated more pharyngeal acid re-
flux events in patients with medically refractory CRS (7/11,
64%) vs healthy controls (2/11, 18%). Pincus et al.412 re-
ported that 25 of 30 patients with refractory CRS had pos- itive pH studies, and 14 of 15 positive pH study patients treated with proton pump inhibitors (PPIs) had improve-
ment of their RS symptoms after 1 month. DiBaise et al.413
found modest improvement in CRS symptoms in 67% of 18 medically and surgically refractory CRS patients after
TABLE VII-3. Evidence for CRS and osteitis as a contributing pathogenic factor
Study Year LOE Study design Study groups Clinical endpoint Conclusions
Saylam400 2009 2b Prospective cohort study CRS patients with and without
osteitis
SPECT scores, subjective evaluation of treatment and prognosis
Poorer subjective scores of patients with higher SPECT scores, presence of osteitis Sethi385 2015 3a Systematic review of
literature
CRS patients Osteitis has been found to correlate with mucosal eosinophilia. Only a suggested association exists of CRS and osteitis Bhandarkar401 2013 3a Systematic review of
literature
CRS patients Osteitis is associated with worse treatment outcomes and with worse disease Georgalas402 2013 3a Systematic review of
literature
CRS patients Correlation between radiologic severity and extent osteitis exists. No correlation between clinical severity and osteitis
Videler386 2011 3a Systematic review of
literature
CRS patients CT is recommended for identification of osteitis. No evidence of bacteria in paranasal sinus bone. Surgery may incite osteitis Chiu384 2005 3a Systematic review of
literature
CRS patients The cause of bone remodeling is unknown
Dong406 2014 3b Prospective cohort study 84 CRS patients undergoing
ESS and 22 control patients
Tissue samples: biofilm volume, biofilm score, histopathologic bony grade, GOSS, and HU value
The rate of osteitis in CRS was higher by CT and by histopathologic grading. Biofilms were associated with osteitis
Wood405 2012 3b Prospective case control CRSsNP (n=8); CRSwNP
(n=8); controls (n=6)
Presence of bacteria and immune cells in bone removed during ESS or skull base surgery
Bacteria colonies and immune cells in bone were identified in similar number of CRS and controls Georgalas403 2010 3b Prospective, case control CRS (n=102) and controls
(n=68) undergoing sinus CTs
GOSS, LM grading scale Osteitis was more common in CRS. Strong correlation between previous surgery and osteitis
Telmesani398 2010 3b Prospective case control CRSwNP (n=82, divided into
primary vs revision surgery
Histopathologic examination of ethmoid bone and mucosa. Disease recurrence
Higher risk of osteitis with worse mucosal pathology and revisions surgery. Osteitis predicted higher recurrence
Cho399 2008 3b Retrospective case control CRS patients having primary
ESS (n=25); CRS patients having revision ESS (n= 15); controls (n=25)
Ethmoid NBF; HU; LM scores; bone thickness on CT
NBF higher in revision cases and higher LM scores. CRS groups had increased bone thickness
Giacchi390 2001 3b Prospective case control CRS patients with ESS (n=
20); controls having CSF leak repair (n=5)
Ethmoid mucosa and bone evaluated by pathology for mucosal and bone changes
Bone resorption and osteoneogenesis noted in CRS
Kennedy391 1998 3b Prospective case control CRS having ESS (n=24);
controls (n=9) undergoing ethmoid surgery
Ethmoid tissue grouped according to histologic appearance of bone and mucosa
Bone remodeling activity was increased in the CRS group compared to controls
TABLE VII-3.Continued
Study Year LOE Study design Study groups Clinical endpoint Conclusions
Snidvongs404 2013 4 Retrospective cohort CRSwNP (53%) and CRSsNP
(47%) patients receiving surgery
CT, histopathology, endoscopy, and QoL measures. KOS, GOSS
51% of patients had osteitis; higher prevalence with revision surgery. No correlation between QoL and osteitis
Snidvongs407 2012 4 Retrospective case study 88 patients with CRSwNP or
CRSsNP undergoing ESS
LM scores histopathology, SNOT-22 scores, asthma, aspirin sensitivity
51% of patients had osteitis; tissue and serum eosinophilia correlated with osteitis
Bhandarkar78 2011 4 Prospective case series 190 patients with CRS
undergoing ESS
LM CT scores, SIT, endoscopy, presence of osteitis on CT, RSDI, CSS
Osteitis correlated with increased age, revision surgery, NPs, asthma, and ASA intolerance, and less postoperative QoL improvement Lee392 2006 4 Prospective case series Patients undergoing ESS for
CRS
Presence of concurrent osteitis based on imaging and histopathology
CT showed osteoneogenesis in 36%, with 53% showing signs of osteitis on pathology Cho389 2006 4 Retrospective case series Patients undergoing primary
ESS for CRS
LM CT scores, HU of ethmoid region on CT,
histopathologic analysis of ethmoid mucosa and bone
HUs increased with higher LM. Histopathologic bony grades increased with higher mucosal grades Kim387 2006 4 Retrospective case series Patients undergoing primary
ESS for CRS
CT scans for evidence of hyperostosis, postoperative endoscopic outcomes
60% of patients showed hyperostosis, associated with poorer postoperative outcome
KOS=Kennedy Osteitis Score; NBF=new bone formation.
6 months of PPI treatment for reflux. Neither the Pincus
et al.412nor the DiBaise et al.413study had a control group.
Ozmen et al.414 showed a higher prevalence of pharyn-
geal reflux events (29/33) and positive nasal pepsin assay (26/33) in medically refractory CRS patients, as compared
to controls (11/20 for each). Loehrl et al.415found positive
pharyngeal pH probes in 19 of 20 surgically refractory CRS patients, and positive nasal pepsin assays were found in all 5 patients tested.
In a prospective case control study, DelGaudio416 re-
ported statistically significant higher incidences of reflux
events in the distal esophagus (p = 0.007), hypopharynx
(p = 0.006), and nasopharynx below pH 4 (p = 0.004)
and pH 5 (p = 0.00003) in 38 surgically refractory CRS
patients as compared to 10 successful ESS patients and 20
normal controls. Wong et al.417 detected over 800 reflux
events at a pH cutoff of<4 in 37 medically refractory CRS
patients who were candidates for ESS: 596 at the distal esophagus, 187 at the proximal esophagus, 24 at the hy- popharynx, and only 2 at the nasopharynx. Based on their results, Wong’s group concluded that nasopharyngeal re- flux is a rare event in CRS, and that the pathophysiology of reflux in CRS is likely an alternative mechanism than
direct contact with nasal mucosa.417Comparing this study
to the DelGaudio study,416 the patients in the cohort in
Wong et al.417 were medically (and not surgically) refrac-
tory CRS patients, thereby resembling the successful ESS control group in the DelGaudio study, having significantly less nasopharyngeal reflux events than the patients with refractory CRS. Another significant difference is that the
pH cutoff in the Wong et al.417 article was<4, which may
have missed reflux events that occurred between pH 4 and 5. The findings in these studies therefore suggest a larger role for reflux directly affecting the nasal mucosa in more severe cases of CRS that are refractory to surgical manage- ment, as compared to less severe CRS cases which can be controlled either medically or surgically.
Jecker et al.418 reported that 20 surgically refractory
CRS patients had significantly more reflux events in the esophagus than 20 healthy control patients. Interestingly, this was not observed in the hypopharynx, suggesting that refractory CRS is associated with gastroesophageal reflux disease (GERD) but not with extra-esophageal
reflux (EER).418 This may suggest a vagally-mediated
response.
Vˇceva et al.410 reported that Helicobacter pylori DNA
was identified in the NP tissue of 10 of 35 study group patients, but it was not detected in the concha bullosa
with normal mucosa specimens of 30 control patients, even
though H. pylori DNA was found in the gastric mucosa
samples of all study and control subjects. Ozdek et al.419
illustrated the presence ofH.pyloriRNA by PCR in 4 of 12
ethmoidal tissue samples in patients with CRS and in none of 13 concha bullosa specimens in patients without CRS.
Although these studies suggest thatH.pyloriis associated
with CRS, evidence of a causal relationship has not been demonstrated.
PND is a symptom frequently attributed to both reflux and RS. In a randomized-controlled double-blind crossover
study of 75 patients with complaints of PND, Vaezi et al.420
reported improvement of symptoms in 50% of patients treated with a PPI compared to 5% in the placebo arm. The authors concluded that these findings support a role for reflux in PND symptoms.
Data in the published literature are frequently conflict- ing. A recent evidence-based approach concluded weak
support for causation between GERD and RS.421 There
is significant evidence demonstrating a coexistent relation- ship between reflux and CRS, although causation cannot be clearly demonstrated. It is not entirely clear with the evidence currently available whether extraesophageal re- flux of gastric acid directly injures the sinonasal mucosa, whether reflux events cause vagally-mediated neuroinflam- matory changes, or if it is a combination of both of these