Análisis Externo

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Cost: Moderate for associated diagnostic testing and pos-

sible consultation.

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Benefits-Harm Assessment: Balance of benefits over

harm.

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Value Judgments: Asthma is highly prevalent in patients

with CRSwNP.

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Policy Level: Recommend.

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Intervention: Asthma screening should be considered in

all patients with CRSwNP.

VIII.C.1. CRSwNP: Pathophysiology

VIII.C.1.a.

CRSwNP Pathophysiology Contribut-

ing Factors: Allergy.

IgE-mediated allergy has been among the multiple etiologies suggested to cause CR- SwNP. Allergy is strongly associated with a Th2-mediated response. Multiple studies suggest a prominent role for Th2-mediated inflammation in the pathogenesis of

CRSwNP.875–880_{Elevated levels of Th2 cytokines IL-5 and}

IL-13 have been isolated in NP tissue and eosinophilic inflammation is commonly identified in both atopy and CRSwNP. In addition, mast cells and basophils are also significantly increased in NPs and their counts correlate with the increased eosinophils in polyp tissue. Inasmuch as mast cells and basophils are the cells involved in IgE-mediated allergic inflammation, their presence suggests that eosinophils, mast cells, and basophils are associated in the ongoing Th2 inflammatory response observed in CRSwNP. This indirect evidence of an association between

TABLE VIII-1. Evidence for CRSwNP and asthma as a comorbidity

Study Year LOE Study design Study groups Clinical endpoint Conclusions

Swierczy ´nska- Kr ˛epa871

2014 1b Prospective randomized trial

1. AERD patients with NPs; 2. Non-AERD patients with NPs

1. Nasal clinical and biochemical parameters; 2. Lung clinical and biochemical parameters

Only patients with AERD had clinically beneficial effects of ASA desensitization on nasal and bronchial symptoms Ehnhage864 _{2009 1b Prospective}

randomized trial

CRSwNP and asthma, after ESS: 1, INCS; 2, placebo

1. Nasal symptoms; 2. Polyp score; 3. Lower airway symptoms

ESS improved nasal and lower airway symptoms. No significant differences between INCS group and placebo

Ragab319 _{2006 1b Prospective}

randomized trial

1. Surgical group (CRSsNP and CRSwNP); 2. Medical group (CRSsNP and CRSwNP)

1. Asthma symptoms and control; 2. FEV1 and peak flow; 3. Medication use; 4. Hospitalization

Improved symptoms in medical group. Improved FEV1. Lower medication needs. Lower

hospitalization rate Vashishta872 _{2013 2a Systematic review CRS patients with at least one}

asthma outcome reported

1. Overall asthma control; 2. Asthma attacks; 3. Number of hospitalizations; 4. Use of oral corticosteroids

ESS in patients with concomitant bronchial asthma improves clinical asthma outcome measures, but not lung function testing Dejima574 _{2006 2b Prospective}

controlled trial

1. CRS with asthma undergoing ESS; 2. CRS without asthma undergoing ESS

1. Lower airway symptoms; 2. Sinonasal symptoms

Improved symptoms. Reduced medication needs. Improved FEV1 Ikeda862 _{1999 2b Prospective} controlled trial 1. CRSwNP undergoing ESS; 2. CRSsNP undergoing ESS

1. Sinonasal and pulmonary symptoms; 2. Medication use

Improved FEV1 and reduced medication needs

Ehnhage867 _{2012 2b Cohort study CRSwNP patients with}

asthma, after ESS

1. Dyspnea/cough scores; 2. Mean daily peak expiratory flow rate; 3. Spirometry; 4. Butanol test; 5. Olfaction score; 6. PNIF; 7. polyps score

Improvement in asthma symptoms score. Improvement in daily peak expiratory flow.

Improvement in all nasal parameters

Uri866 _{2002 2b Prospective cohort CRSwNP and asthma patients}

undergoing ESS

1. Asthma and nasal symptoms; 2. Spirometry; 3. Medication use

Improved symptoms. Lower medication needs. No changes in FEV1 Lamblin873 _{2000 2b Prospective cohort CRSwNP and asthma patients}

followed for 4 years

1. Nasal symptoms; 2. Lower airway clinical and biochemical parameters

CRSwNP patients requiring surgery developed nonreversible airflow obstruction during the observation period Senior874 _{1999 2b Prospective cohort CRS with asthma undergoing}

ESS

1. Symptoms score; 2. Asthma exacerbations; 3. Medication use

Improved symptoms. Fewer asthma relapses. Lower medication needs Nishioka865 _{1994 2b Prospective cohort CRSwNP and asthma patients}

undergoing ESS

1. Symptoms score; 2. Medication use; 3. Number of emergency visits

Improved symptoms

Zhang868 _{2014 4 Retrospective case}

series

Adults with CRS after ESS SNOT-22 CRS patients with both asthma and NP have a larger QoL benefit after ESS than CRS patients without asthma or polyps

TABLE VIII-1.Continued

Study Year LOE Study design Study groups Clinical endpoint Conclusions

Batra861 _{2003 4 Retrospective case}

series

CRSwNP and asthma patients after ESS

1. Symptoms score; 2. Medication use; 3. Number of emergency visits; 4. FEV1 change

Improved symptoms. Lower medication needs. Lower number of emergency visits. Improved FEV1 Dunlop320 _{1999 4 Retrospective case}

series

1. CRSwNP and asthma patients after ESS; 2. CRSsNP and asthma patients after ESS

1. Symptoms score; 2. Medication use; 3. Number of emergency visits; 4. FEV1 change

Improved symptoms. Lower medication needs. Lower hospitalization rates. Improved FEV1

allergy and CRSwNP is not, however, confirmed with direct clinical evidence, where the data are often unclear or contradictory.

In 2014, Wilson et al.322 _{reviewed the role of allergy in}

CRSwNP and CRSsNP. They considered only studies that delineated the presence of polyps or not, so that studies examining “CRS” alone were excluded. In both CRSsNP and CRSwNP, they found the aggregate LOE linking al- lergy to these forms of CRS to be level D, due to conflicting prevalence data, complemented by expert opinion and reasoning from first principles. In CRSwNP specifically, they found 18 epidemiologic studies that addressed the role of allergy in CRSwNP. Ten of these studies (1 level 2b, 9 level 3b) supported an association, 7 (3 level 3b, 4 level 4) did not, and 1 (level 3b) was equivocal.

Tan et al.881 _{found a higher number of inhalant sen-}

sitivities in CRSwNP patients compared to CRSsNP and rhinitis patients, although the overall sensitivity rates were

similar. Houser and Keen882_{evaluated for allergy using in-}

tradermal testing or radioallergosorbent testing in surgical CRSwNP and CRSsNP patients. In CRSwNP patients, a statistically significant association was identified only for perennial allergens, most notably dust mites. Similarly,

Asero and Bottazzi883 _{identified higher prevalence of dust}

mite sensitivity in polyp patients when compared with

non-polyp counterparts. Munoz del Castillo et al.884

further implicated dust mite allergy in CRSwNP patients. Using skin-prick testing, they found 63.2% had at least 1

positive result, most frequently to dust andOlea europaea.

Pumhirun et al.885 _{found elevated dust and cockroach in}

CRSwNP. Asero and Bottazzi886_{found positive skin testing}

to at least 1 fungal species at higher rates in CRSwNP patients when compared to both allergic controls and CRSsNP patients. Among these patients, the only genus to

reach statistical significance wasCandida.

Other studies have not found a significant association between CRSwNP and allergy based on either rates of

sensitivity or disease outcomes. Pearlman et al.887_{found no}

significant difference in atopic rates between CRSwNP and

CRSsNP groups. Keith et al.888_{found that ragweed-allergic}

CRSwNP patients did not have worse symptoms during

the ragweed season. Erbek et al.889 _{divided patients with}

CRSwNP by atopic status. No difference was identified

in NP size, CT scores, symptoms, or recurrence of disease

based on atopic status.889 _{Similarly, Bonfils’ group}890, 891

did not identify any difference in the presenting symptoms or postoperative course of CRSwNP patients regardless of their allergic status.

Contradictory results in these studies likely reflect differ- ences in study design, inclusion criteria, and populations studied. Taken together, these data suggest that inhalant allergy may be a disease-modifying factor in CRSwNP, but a direct link to causation is lacking.

Taking the totality of these studies into account, Wilson

et al.322_{concluded that allergy testing should be considered}

an option in CRSwNP patients, inasmuch as there was a theoretical benefit of finding inflammatory triggers, there is little harm, and the low aggregate LOE did not support a strong recommendation either for or against this practice.

Although food allergies have been postulated to play a role in CRSwNP, there is no evidence that substantiates this view. A few studies show higher sensitization rates to foods in patients with CRSwNP compared to controls, but

the clinical implications are not known.892, 893

Despite an overlap of immunologic pathways and of symptoms, conflicting data in the literature prevents defini- tive conclusion about the association between atopy and nasal polyposis. Well-designed, prospective studies with defined inclusion and exclusion criteria among defined pop- ulations should shed additional light on this relationship.

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Aggregate Grade of Evidence: D (Conflicting observa-

tional studies—case control and cohort design).

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Benefit: Management of allergy symptoms is low risk

and may reduce 1 potential source of inflammation con- tributing to CRSwNP.

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Harm: Discomfort from allergy testing, sedation from

oral antihistamine, epistaxis from INCS.

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_{Cost: Direct costs: diagnostic testing and treatment. Indi-}

rect costs: time off work for immunotherapy, decreased productivity during peak allergy seasons.

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Benefits-Harm Assessment: Low-risk treatment to

achieve improvements in allergic symptoms and QoL.

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Policy Level: Option.

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Value Judgments: Allergy testing and treatment (avoid-

ance, medication, immunotherapy) are an option for pa- tients with CRSwNP.

VIII.C.1.b.

CRSwNP Pathophysiology Contribut-

In document Modelo de negocio para el restaurante Simón 7 84 para el período 2019 – 2021 (página 57-67)