Main Findings from Retrospective Studies on the Comorbidity of Asthma and Sinusitis and Their Implications for Clinical Practice

Abstract

Asthma and chronic rhinosinusitis (CRS) are prevalent chronic inflammatory conditions of the airways that frequently occur together, contributing to increased disease burden and reduced quality of life. This study aimed to synthesize findings from retrospective research to better understand the clinical and pathophysiological interrelations between these two conditions. A narrative review was conducted, including studies (2002–2025) assessing prevalence, lung function, biomarkers, quality of life, and treatment outcomes in patients with confirmed asthma and/or CRS. The results revealed a high prevalence of comorbidity, particularly in patients with CRS with nasal polyps (CRSwNP), where asthma co-occurrence exceeds 50% in certain phenotypes. Shared type 2 inflammatory mechanisms, including eosinophilic infiltration, cytokine overexpression (IL-4, IL-5, and IL-13), and tissue remodeling via matrix metalloproteinases, were frequently identified. These findings support the unified airway model and highlight the systemic nature of inflammation in these patients. Biologic therapies demonstrated effectiveness in reducing exacerbations and improving clinical outcomes, especially in patients with more severe phenotypes. The inclusion of dentistry and oral health as components of the systemic inflammatory burden offers an innovative perspective and reinforces the importance of holistic, interdisciplinary care. This study underscores the need for a multidisciplinary, phenotypically guided approach to treatment. Recognizing and systematically addressing this comorbidity can improve disease control and enhance patient quality of life.

1. Introduction

Bronchial asthma and chronic rhinosinusitis (CRS)—including phenotypes with and without nasal polyps (CRSwNP and CRSsNP)—are chronic inflammatory diseases of the respiratory tract that carry a high global prevalence and impose significant burdens on the quality of life. Over the past decades, a growing body of evidence has revealed a strong bidirectional association between these conditions. While it is well established that asthma is common among patients with CRS, affecting up to 60% of those with CRSwNP and approximately 23.8% of those without CRSsNP [1], less frequently highlighted is the inverse perspective: CRS is also prevalent among individuals with asthma. Studies suggest that between 30% and 50% of asthma patients have concomitant CRS, and the prevalence is even higher in those with severe or late-onset asthma [2,3].

This reciprocal relationship reflects a complex interplay of shared inflammatory pathways, anatomical proximity, and overlapping clinical manifestations. The unified airway theory, supported by histological and immunological findings, proposes that the upper and lower airways operate as a single integrated unit [4,5]. Eosinophilic inflammation, driven by cytokines such as IL-5 and IL-13 and modulated by matrix metalloproteinases, characterizes both disorders. Mediators released in the paranasal sinuses can exacerbate bronchial inflammation via systemic dissemination or retrograde aspiration, complicating asthma control and management [6,7].

Clinically, this comorbidity results in more severe disease expression. Patients with both asthma and CRS often report intensified respiratory symptoms, increased exacerbation rates, greater reliance on systemic corticosteroids, and poorer pulmonary function outcomes [8,9]. Radiologic markers, such as the Lund–Mackay score, are positively associated with spirometric decline, particularly among patients with chronic cough and uncontrolled asthma [7]. Beyond respiratory symptoms, this association also contributes to chronic pain, impaired sleep, and diminished overall quality of life [10]. Notably, late-onset asthma linked with CRS tends to exhibit greater severity and reduced responsiveness to conventional treatments [11].

Given the substantial prevalence, clinical burden, and overlapping pathophysiology of these conditions, there is a pressing need to enhance our understanding of their interconnection. Despite advances in targeted therapies and growing recognition of shared immunologic pathways, current clinical guidelines often fall short in addressing this comorbidity holistically. Retrospective data can offer valuable insights into epidemiological trends, risk stratification, biomarker discovery, and optimized therapeutic approaches.

In this context, the primary aim of this narrative review is to synthesize retrospective evidence on the comorbidity of asthma and CRS, highlighting prevalence patterns, pathophysiological mechanisms, and therapeutic implications. To address this, we analyze epidemiological, pathophysiological, and therapeutic evidence supporting the integrated management of these interconnected diseases.

2. Materials and Methods

2.1. Search Strategy

A narrative literature review was performed using three electronic databases: Pubmed, Scielo, and Web of Science. The search focused on publications From January 2022 to March 2025, in English, Portuguese, or Spanish.

The search strategy combined Mesh terms and free-text keywords related to asthma and chronic rhinosinusitis (CRS). The following boolean structure was used, with variations depending on the database: (“asthma” AND “chronic rhinosinusitis”) AND (“comorbidity” OR “association”) AND (“airway inflammation” OR “type 2 inflammation”) AND (“nasal polyps” OR “CRSwNP”) AND (“biologics” OR “biological therapy”) AND (“quality of life” OR “pulmonary function” OR “therapeutic outcomes”).

Each of these thematic elements was not used in separate searches but rather as part of combined queries to ensure comprehensive retrieval of relevant studies. For instance, “therapeutic outcomes” was not a standalone search term but was included in broader combinations targeting outcomes of biological therapy or quality-of-life improvements in asthma-CRS patients. Similarly, while “allergic rhinitis” was not used as a primary search term, studies that discussed it in relation to asthma–CRS comorbidity or as a modifying factor were included if they contributed relevant pathophysiological or clinical insights. This decision was made to capture a broader but still focused understanding of airway inflammation across the upper and lower respiratory tract.

We also manually screened references from included articles to identify additional relevant studies.

2.2. Search Strategy

The initial search yielded approximately 90 articles across all three databases. After removing duplicates and screening titles and abstracts, 45 articles were selected for full-text evaluation. Of these, 31 articles met eligibility criteria and were included in the review.

Although 31 studies were referenced throughout the article for contextual and theoretical support, the main results and synthesis presented in Section 3 are drawn from 10 core retrospective studies that specifically met all inclusion criteria and contributed primary data relevant to prevalence, biomarkers, pulmonary function, and therapeutic outcomes.

2.3. Inclusion Criteria

We included

• retrospective cohort studies, observational studies, and systematic reviews;
• Studies with sample sizes > 30;
• Population with confirmed diagnosis of asthma and/or CRS, including both CRSwNP and CRSsNP;
• Studies evaluating at least one of the following: prevalence, pulmonary function, biomarkers, quality of life, or treatment outcomes.

2.4. Quality Assessment

Although this is a narrative review, we follow a simplified critical appraisal approach:

• Study design and level of evidence;
• Sample representativeness;
• Diagnostic clarity for asthma and CRS;
• Presence of control/comparison groups when applicable;
• Use of validated outcome measures (e.g., ACT, SNOT-22, FEV₁, biomarkers);
• Transparency in reporting imitations and potential cofounders.

Specifically, for asthma, we considered studies that used clinical diagnosis supported by spirometry with reversible airflow limitation or referred to established diagnostic frameworks such as the Global Initiative for Asthma (GINA) guidelines. For CRS, we accepted diagnostic confirmation based on symptoms lasting ≥12 weeks, endoscopic evidence of nasal inflammation, or radiological findings consistent with CRS, aligning with criteria outlined in the EPOS 2020 guidelines. Studies that did not specify objective diagnostic methods or failed to differentiate CRS phenotypes (e.g., CRSwNP vs. CRSsNP) were excluded. Studies with unclear diagnostics, very small samples, or high risk of bias were excluded. This process allowed for an evidence-informed synthesis even without a formal systematic review protocol.

3. Results

3.1. Prevalence of Comorbidity

The association between chronic rhinosinusitis (CRS) and asthma has been shown to be highly prevalent in retrospective studies, emphasizing the need for systematic evaluation of this comorbidity in patients with poorly controlled asthma. According to Kang et al. (2024) [1], approximately 23.8% of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) also had asthma. In contrast, in cases with nasal polyps (CRSwNP), asthma prevalence ranges from 48% to 60% [12]. In more severe phenotypes, such as late-onset CRSwNP, the association exceeds 50% of cases [11]. Allergic rhinitis affects approximately 400 million people globally, while asthma affects over 300 million people and results in over 495,000 fatalities each year [13].

These data are summarized in

Table 1. Asthma Prevalence in Different Phenotypes of Chronic Rhinosinusitis.

Study	CRS Type	Asthma Prevalence (%)	Notes
Kang et al. (2024) [1]	CRSsNP	23.8%	Without polyps
Wechsler et al. (2024) [12]	CRSwNP	48–60%	With polyps
Staniorski et al. (2023) [11]	CRSwNP (late-onset)	>50%	Greater clinical severity
Sousa et al. (2020) [10]	CRSwNP (severe asthma)	Not quantified	High comorbidity in severe asthma

.

3.2. Risk Factors and Pathophysiological Mechanisms

Several risk factors have been consistently associated with the comorbidity of asthma and rhinosinusitis, including allergic rhinitis, peripheral eosinophilia, elevated total IgE, female sex, and advanced age [14]. The pathophysiological mechanisms linking these conditions suggest a common inflammatory basis, especially type 2 inflammation, characterized by increased cytokines such as IL-4, IL-5, and IL-13. The co-existence of asthma and rhinosinusitis is not merely coincidental but rather reflects a shared mucosal susceptibility to exogenous stimuli, indicating that rhinosinusitis and asthma represent systemic, rather than merely localized, inflammatory processes affecting the respiratory tract [3]. Overlapping inflammatory pathways, altered interoceptive perception, and shared psychosocial stressors are all examples of hypotheses that may explain these connections [15]. Disrupting commensal fungi can affect both local and peripheral immune responses and enhance disease states [16]. Like the GI tract, the respiratory tract is composed of distinct environments that vary according to mucosal architecture and immune responses [16]. The interplay between the upper and lower respiratory tracts is encapsulated in the “unified airway” or “one airway, one disease” paradigm, which proposes that inflammatory processes in one anatomical location can exert influence over the other, potentially manifesting through direct propagation of inflammatory mediators or indirectly via systemic pathways [3]. The involvement of both the upper and lower airways has a substantial influence on patients’ quality of life [17].

Table 2. Shared Pathophysiological Mechanisms between Asthma and Rhinosinusitis.

Mechanism	Description	References
Eosinophilic inflammation	Mediated by IL-5, IL-4, IL-13; common in type 2 inflammation	Okano et al., 2015; Wechsler et al., 2024 [5,12]
MMPs (Matrix Metalloproteinases)	Tissue remodeling and epithelial dysfunction	Kostamo et al., 2007 [4]
Retrograde aspiration	Sinus secretions reach the bronchi, worsening inflammation	Facchin & Kuhl, 2007 [9]
Naso-bronchial reflex	Nasal neural stimulus triggers bronchoconstriction	Kang et al., 2024 [1]
Systemic inflammation	Circulating mediators such as calprotectin worsen asthma	De Corso et al., 2024 [18]

summarizes the main shared mechanisms. Highlights include eosinophilic inflammation, tissue remodeling mediated by matrix metalloproteinases (MMPs), retrograde aspiration of sinus secretions, and the naso-bronchial reflex, which can trigger bronchospasm via neural stimulation. Additionally, biomarkers such as serum calprotectin and IL-5 have been correlated with disease severity in patients with CRSwNP and asthma [18].

3.3. Functional Impact and Quality of Life

The coexistence of asthma and CRS significantly worsens the patient’s quality of life. Kariya et al. (2014, 2015) [6,7] demonstrated correlations between high Lund–Mackay scores and obstructive respiratory symptoms. Patients with both conditions also report increased facial pain, fatigue, functional impairment, and social isolation [8,10], highlighting the systemic burden of chronic inflammation. Although not the primary focus of this review, allergic rhinitis (AR) is frequently discussed in the literature as a modifier of disease burden in patients with asthma and CRS, due to overlapping inflammatory pathways and symptom overlap. According to EPOS 2020 and Georgalas et al. (2014) [19], AR can contribute to increased nasal congestion, sleep disturbances, and lower airway hyperresponsiveness, thereby worsening overall quality of life in multimorbid patients. While the role of AR remains partially controversial in unified airway models, its contribution to symptom amplification in CRS–asthma overlap cannot be entirely disregarded, especially in type 2 inflammatory phenotypes [19,20]. The respiratory epithelium, which provides a physical and immunological barrier against inhaled environmental particles, is essential for preserving host health. Compromised respiratory epithelium can trigger immune and inflammatory responses against allergens and pollutants, increasing the risk of chronic inflammation in conditions like allergic rhinitis, chronic rhinosinusitis, and asthma [21]. Chronic rhinosinusitis, characterized by persistent inflammation of the nasal and paranasal sinus mucosa, represents a significant public health concern, affecting a substantial proportion of the adult population in the United States and leading to a notable reduction in overall well-being and considerable economic strain on healthcare systems [22].

3.4. Therapeutic Efficacy

Therapeutic interventions have proven effective in managing both diseases simultaneously. The use of topical nasal corticosteroids, endoscopic sinus surgery (ESS), and particularly biologic therapies has shown substantial benefits for patients with severe asthma and CRS [14]. Biologic agents such as mepolizumab, dupilumab, and omalizumab have reduced exacerbations, improved lung function, and lowered systemic corticosteroid use [12].

Interestingly, the presence of other atopic comorbidities like allergic rhinitis and atopic dermatitis, although common, did not significantly influence outcomes related to biologic therapy. Moreover, patients with CRS—especially with polyps—responded better to these agents, reinforcing the importance of individualized phenotypic approaches. This enhanced responsiveness in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) may be attributed to the shared type 2 inflammatory pathway, which is characterized by elevated levels of eosinophils and cytokines such as IL-4, IL-5, and IL-13. Biologics targeting these cytokines not only help control asthma symptoms but also reduce polyp size and nasal congestion, contributing to a significant improvement in quality of life. Clinical trials have demonstrated that dupilumab, an IL-4Rα antagonist, yields marked benefits in patients with comorbid asthma and CRSwNP, including reductions in nasal obstruction, improvement in smell, and fewer asthma attacks [23,24,25,26,27,28].

Furthermore, ESS, while primarily aimed at improving sinus ventilation and drainage, has also been associated with secondary respiratory benefits in asthma patients. Postoperative improvements in asthma control and reduced medication dependency have been observed, especially when surgery is followed by optimal medical management, including corticosteroids or biologics. This highlights the value of a multidisciplinary treatment strategy involving both pulmonologists and otolaryngologists.

The evolving landscape of biologic therapies also suggests the potential for biomarker-driven treatment plans. Identifying patients allergists (e.g., eosinophilic vs. non-eosinophilic) can help optimize therapeutic outcomes and minimize unnecessary exposure to systemic drugs. Thus, current evidence strongly supports the integration of precision medicine into the therapeutic algorithm for patients with asthma-CRS overlap, maximizing efficacy while reducing adverse effects.

Finally, a multidisciplinary management approach is essential, involving pulmonologists, otolaryngologists, allergists, dentists, and general practitioners, with a focus on reducing hospitalizations and improving quality of life.

4. Discussion

The association between asthma and chronic rhinosinusitis (CRS) is supported by a complex interplay of inflammatory, structural, and immunological mechanisms. The unified airway concept proposes that the upper and lower airways function as a continuum, where inflammation in one region can trigger or worsen manifestations in the other [2,3]. This review reinforces that interdependence, highlighting high asthma prevalence, particularly in patients with CRSwNP, as shown in Table 1.

The predominant pathophysiological axis appears to be type 2 inflammation, marked by eosinophilic infiltration and overexpression of cytokines such as IL-5, IL-4, and IL-13 [5,12]. These mediators contribute to tissue remodeling, increased mucus production, and bronchial hyperresponsiveness. Notably, eosinophilic infiltration in the paranasal sinuses has been associated with asthmatic symptoms even in the absence of typical respiratory signs, suggesting a subclinical systemic inflammatory state [6].

Furthermore, biomarkers such as matrix metalloproteinases—particularly MMP-9—play a significant role in extracellular matrix degradation and epithelial dysfunction and are associated with more severe phenotypes of CRS and asthma [4]. Such patients tend to respond better to biologic therapies, reinforcing the value of inflammatory phenotyping in guiding treatment decisions.

Other relevant mechanisms include retrograde drainage of infected sinus secretions into the lower airways, potentially worsening bronchial inflammation and contributing to asthma control issues [9]. The naso-bronchial reflex represents a neurogenic interaction pathway where local stimuli can trigger bronchoconstriction via vagal reflexes [1].

Systemic inflammation also plays a central role in this comorbidity. Elevated serum levels of mediators such as calprotectin have been associated with greater disease severity and poorer control, indicating that CRS may sustain bronchial inflammation in asthmatic individuals [18]. These mechanisms, summarized in Table 2, provide a rationale for using biologics targeting shared inflammatory pathways.

In terms of treatment, the literature indicates that the presence of CRS, especially with nasal polyps, correlates with better responses to monoclonal antibodies like mepolizumab, dupilumab, and omalizumab. These agents significantly reduce exacerbation rates, improve lung function, and decrease the need for oral corticosteroids in severe asthma patients [12]. This supports the importance of an integrated approach to upper and lower airway assessment and treatment.

The integration of dentistry into the management of chronic respiratory diseases such as asthma and CRS is a clinically relevant strategy, although still underrepresented in interdisciplinary guidelines. Studies have shown that inflammatory oral conditions, such as periodontitis, may worsen respiratory diseases through common immunoinflammatory pathways, including systemic elevations of cytokines like IL-1β, IL-6, and TNF-α, which are also involved in the pathophysiology of asthma and CRS [29,30]. Chronic mouth breathing, common in individuals with persistent nasal obstruction, is associated with craniofacial development alterations, increased risk of dental caries, halitosis, and TMJ disorders, impacting both oral health and overall quality of life [30]. In this context, dentists play a crucial role in early detection of oral manifestations related to respiratory disease and treatment, as well as in patient education for preventing complications associated with inhalation devices and systemic medications.

Therefore, the role of dental professionals should be integrated into multidisciplinary teams managing patients with comorbid asthma and rhinosinusitis. This collaborative approach may not only minimize secondary oral manifestations of respiratory treatment but also contribute to reducing systemic inflammatory burden, enhancing therapeutic outcomes, and improving quality of life.

Emerging evidence supports the view that poor oral health—particularly periodontal disease and chronic oral inflammation—can amplify systemic inflammatory burden and contribute to the pathogenesis or exacerbation of chronic respiratory diseases. Shared immunopathological mediators, including IL-1β, IL-6, and TNF-α, are elevated in both periodontal disease and airway inflammation, suggesting overlapping biological pathways. Furthermore, mouth breathing, often secondary to chronic nasal obstruction in CRS, predisposes patients to dental caries, halitosis, and structural changes in the oral cavity, such as malocclusion or temporomandibular joint (TMJ) dysfunction. These conditions not only degrade oral health but may indirectly worsen respiratory outcomes by promoting chronic systemic inflammation and impaired upper airway function. Including dental professionals in multidisciplinary care teams could facilitate earlier detection of oral manifestations, improve patient education on inhaler hygiene, and potentially mitigate inflammation across systems. This underscores the need for interdisciplinary protocols that recognize the bi-directional influence between oral and respiratory health [29,30,31].

The importance of integrated upper and lower airway assessment is also emphasized in the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020), which recognizes the frequent coexistence of CRS and asthma and recommends coordinated, phenotype-driven management for optimal outcomes [26]. The 2025 GINA guidelines recognize the united airway model and emphasize the importance of assessing and managing upper airway diseases, including chronic rhinosinusitis and allergic rhinitis, in patients with asthma. GINA specifically recommends that clinicians evaluate for upper airway comorbidities in patients with difficult-to-control or severe asthma and treat them as part of a holistic asthma management plan. Addressing upper airway inflammation can lead to better asthma control, fewer exacerbations, and improved quality of life. Treatment strategies endorsed by GINA include the use of intranasal corticosteroids, biologic agents targeting type 2 inflammation (e.g., anti-IL-5, anti-IL-4R therapies), and multidisciplinary care coordination between pulmonologists and ENT specialists. This aligns with our findings and reinforces the clinical relevance of integrated, phenotype-driven care in patients with coexisting asthma and CRS.

Despite the growing body of evidence supporting the unified airway model and the efficacy of biologic therapies, several limitations must be acknowledged. Many of the studies included in this review are observational or derived from post hoc analyses of randomized trials, which limits causal inference and generalizability. Furthermore, clinical trials on biologics often include highly selected populations, excluding patients with overlapping comorbidities or less defined inflammatory profiles. This restricts our understanding of real-world effectiveness in more diverse and complex patient populations, such as those with non-type 2 inflammation or overlapping infectious phenotypes.

Another critical limitation lies in the diagnostic heterogeneity of CRS, particularly when comparing patients with and without nasal polyps (CRSwNP vs. CRSsNP). While CRSwNP is more consistently associated with type 2 inflammation and better response to biologics, the pathophysiological mechanisms and optimal treatment strategies for CRSsNP remain less clear and underexplored. Additionally, the lack of standardized biomarkers to guide phenotypic classification and therapeutic decisions still poses a major challenge in clinical practice. Also, lack of standardized diagnostic tools for CRS across different healthcare systems.

There is also a need to address areas of ongoing controversy. For example, while the use of ESS has been shown to improve asthma control in selected patients, its long-term impact on systemic inflammation remains debatable, and there is no consensus on the optimal timing of surgery in the therapeutic algorithm. Moreover, the exact role of oral health in the modulation of respiratory disease severity, although biologically plausible, is based mostly on cross-sectional or retrospective studies, which preclude definitive conclusions about causality.

Future research should prioritize longitudinal and interventional studies that assess the impact of integrated airway management—including dental evaluation—on systemic inflammation and disease control. The development of unified clinical guidelines incorporating multidisciplinary care, including pulmonology, otolaryngology, immunology, and dentistry, is essential to address these gaps. Additionally, greater investment in translational research focused on identifying novel biomarkers and elucidating the interplay between oral and airway inflammation could lead to more personalized and effective therapeutic strategies.

In conclusion, while current evidence supports a strong interrelationship between asthma and CRS—particularly in the context of type 2 inflammation—there remain substantial gaps in knowledge regarding optimal management strategies, especially in patients with mixed phenotypes or comorbid conditions. Bridging these gaps will require a concerted effort to refine diagnostic criteria, validate predictive biomarkers, and foster interdisciplinary collaboration aimed at improving clinical outcomes.

5. Conclusions

This narrative review synthesized retrospective evidence on the comorbidity of asthma and chronic rhinosinusitis (CRS), emphasizing prevalence, functional impact, inflammatory mechanisms, and therapeutic implications. The findings confirm that this overlap is not incidental but reflects shared type 2 inflammatory pathways and a clinically relevant disease cluster with significant impact on quality of life, exacerbation rates, and treatment responsiveness.

Importantly, the review highlights that while the association between CRS and asthma is well established, the translation of this knowledge into clinical practice remains incomplete. Current evidence supports the integration of CRS management into asthma care, particularly in severe or late-onset phenotypes where comorbidity is most prevalent. Retrospective studies consistently show that addressing upper airway inflammation, through surgery, intranasal corticosteroids, or biologic therapies, can improve asthma control, underscoring the need for multidisciplinary management.

Guideline frameworks, such as EPOS 2020 and GINA 2025, already advocate for this “united airways” approach, but its adoption in daily practice is inconsistent. Therefore, our review identifies a clear gap: the need for greater implementation of phenotype-driven, guideline-based strategies, supported by biomarkers and integrated care models.

Future research should prioritize prospective studies that validate the impact of unified airway management on long-term outcomes, while also exploring under-investigated areas such as the role of oral health, endotypic biomarkers, and the timing of biologic initiation.

In summary, this review consolidates retrospective evidence to provide a foundation for practical, multidisciplinary strategies that can improve disease control in patients with asthma–CRS overlap.