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20426984, 2021, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22741 by Stanford University, Wiley Online Library on [01/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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Orlandi et al.

AECRS, include body mass index, asthma, hay fever, sinus surgery history, and winter season consistently predicting increased AECRS. 212 AECRS also occurs less frequently when asthma is well controlled in asthmatic CRS patients, independent of CRS symptom severity. 29 These risk factors taken together with the first principles underlying ARS and CRS pathophysiology suggest that AECRS is due to an imbalance of host defense and environmental factors sim ilar to the pathophysiology of ARS and some of the same pathophysiological processes associated with CRS. Bacterial overgrowth and infection contribute to acute exacerbations and acute purulent episodes in the sce nario of underlying chronic inflammatory changes associ ated with CRS. The frequent presence of biofilm-forming organisms represents a large reservoir for opportunis tic infections. 1752 However, the low number of studies, the diversity of the different study cohorts, and the lack of a universal definition of AECRS make it difficult to draw any conclusion concerning the role of bacteria in AECRS. Clinical experience suggests antibiotics that cover the most common organisms associated with both ARS and CRS are likely effective in reducing the symptoms of the AECRS. This again points to some role for bacte ria in AECRS, though the antibiotic effects may be alter ing the immune response in addition to their antimicro bial properties. However, 1 randomized, controlled trial failed to show a difference in outcomes in patients receiv ing antibiotics vs placebo. Patients with AECRS received amoxicillin-clavulanate or placebo for 2 weeks. There was no difference in the clinical course between the treatment and control groups. Both groups exhibited overall improve ment of symptoms on day 14 compared to day 0. 211 Brook et al. compared organisms isolated from the max illary sinus of patients with CRS with those suffering from an AECRS. 1753 The identified organisms were predomi nantly anaerobic and similar to those generally identified in CRS ( Prevotella, Porhyromonas, Peptostreptococcus , and Fusobacterium subspecies). However, in addition to the predominance of the anaerobic organisms, aerobic bacteria that are usually found in acute infections were also cultured. Streptococcus pneumoniae and Haemophilus influenzae were found more frequently in patients with AECRS compared to those with CRS without frequent acute exacerbations. It is known that bacterial infection further leads to Th1 and Th2 responses resulting in activa tion of neutrophils and secondarily eosinophils in many cases. 1754 Disturbance of the host mucosal immune system may also play an important role in AECRS. Immunologic changes at the level of receptors, cytokines, interleukins and other mediators, including MCC, is considered cru cial for the basic “first line of defense” of the res piratory mucosa. Rank et al. performed a pilot study

and endoscopic score after surgery; all patients weaned off oral corticosteroid; no

comparison arm.

TABLE X-33 Evidence for AFRS management with anti-IgE Study Year LOE Study Design Study Groups Clinical Endpoint Conclusions Mostafa 1643 2019 2 RCT AFRS patients within 2 weeks of ESS: Single SC omalizumab (150mg) Topical steroids twice daily SNOT 22 scores TNSS scores Total IgE levels Endoscopic score Significantly lower IgE level for omalizumab arm @ 12 weeks but none at 24 weeks; no difference in endoscopic score; Significant improvement in SNOT and TNSS favoring omalizumab.

Decrease in SNOT-22, IgE

Use of corticosteroids or antifungals SNOT 22 score

Endoscopic score

moderate to severe asthma receiving omalizumab

Gan 1742 2015 4 Retrospective review AFRS patients with