Chronic rhinosinusitis with and without nasal polyps: the state-of-the-art of current treatment strategies and future developments

Emanuele Nappi¹Valentina Marzio²Francesco Giombi³Giulia Costanzo⁴Stefania Merli⁵Selene Nicolosi⁶Edoardo Cavaglià³Fabio Lodi Rizzini⁷Serena Traversi⁷Alessandro Vrenna⁷Sofia Vassallo⁸Gian Marco Pace³Carlo Lombardi⁹Carlo Maria Rossi¹⁰FRANCESCA PUGGIONI³Luca MALVEZZI³Giorgio Walter Canonica³Giovanni Paoletti^1,2*Enrico Heffler¹

• ¹Humanitas University, Milan, Italy
• ²Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano (MI), Italy
• ³IRCCS Humanitas Research Hospital, Rozzano, Italy
• ⁴Universita degli Studi di Cagliari, Cagliari, Italy
• ⁵Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
• ⁶Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy
• ⁷Universita degli Studi di Brescia, Brescia, Italy
• ⁸Ospedale Civico Palermo, Palermo, Italy
• ⁹Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy
• ¹⁰Universita di Pavia, Pavia, Italy

Over the past decade, chronic rhinosinusitis (CRS) management has undergone substantial transformation, shifting from conventional symptom-focused treatments to precision medicine strategies grounded on molecular insights. The introduction of biologic agents has significantly changed the therapeutic landscape for CRS with nasal polyps (CRSwNP), directly addressing key inflammatory pathways and leading to marked reductions in nasal polyp burden, overall disease This is a provisional file, not the final typeset article impact, and corticosteroid use. Concerns regarding long-term effectiveness, financial burden, and accessibility remain unresolved. Advances in the understanding of the mechanisms underlying CRS are paving the way for the development of novel therapeutic strategies, with increasing attention now also being directed toward the phenotype without nasal polyps (CRSsNP), which currently lacks targeted therapies. Despite progress in pharmacologic therapies, surgery remains a fundamental treatment option, with ongoing efforts to standardize surgical approaches and evaluate novel techniques. Optimizing the integration of surgical and medical therapies while expanding access to novel treatments represents a key future goal in CRS care. This review aims to guide researchers and clinicians through the evolving landscape of CRS management, covering the latest evidence on established and emerging therapies, offering practical insights into endotyping, and highlighting important considerations for the management of severe or refractory cases.