Are Rhinitis and Asthma Just One Disease Affecting Different Parts of the Respiratory Tract?

Abstract

Both allergic rhinitis and chronic rhinosinusitis with or without nasal polyps have important factors in common with asthma. They are often present simultaneously, they have similar pathogenesis processes, and they have synergistic effects on the clinical manifestations. There are also important considerations regarding the common treatment of these pathologies. Taking all these into account, it is possible to place these diseases under the “united airway disease” umbrella. However, matters such as embryologic origins, anatomy and function of the upper and lower airways, as well as cases where the aforementioned pathologies can be observed independently and have different treatment responses, make up reasonable counterarguments for the “united airway disease”. This narrative review attempts to put all these factors into perspective for a slightly better understanding of the complexity of this topic. We will take into consideration factors such as epidemiological data, pathogenesis and pathology, clinical considerations, and the benefits of a common treatment.

1. Introduction

Before the industrialization that started during the 17th century, allergic diseases were rare and isolated cases, whether they came in the form of rhinitis, asthma, food allergies, or atopic dermatitis [1]. Currently, the modern world is facing an epidemic of allergic diseases. A study from 2019 based on a comprehensive global analysis that utilized standardized data modeling from the Global Burden of Disease Study, covering 204 countries and territories, estimates that asthma alone is affecting 262 million people [2] (even though the study may be limited by regional data gaps and reporting inconsistencies). Another review from 2022 based on a synthesis of international prevalence studies estimated that 30% of adults suffer from a form of rhinitis, most of which likely have an allergic pathophysiological mechanism [3] and possibly a childhood onset. In the USA alone, over 7% of children and 10% of adults suffer from at least one food allergy, according to a global review that is, however, challenged by a lack of standardized diagnostic approaches [4]. These numbers are only expected to rise as time goes on.

The more recent theory explaining the occurrence of these events is that industrialization has caused significant lifestyle and alimentation changes in the population, which in turn heavily impacted the microbiome in the gut and airways. The increase in some types of bacteria and the decrease in others has been associated with an increased likelihood of asthma development in children [5,6,7], while children who live in less modern conditions have a richer microbiome, meaning an overall lower chance of developing allergies.

While most allergic diseases do not pose an imminent threat to the life of the average patient, the impact on a person’s quality of life (QoL) is significant. A 2019 study found that patients with asthma and other allergies have a significantly reduced quality of life, based on an analysis of patient-reported outcomes from a large U.S. population, using validated health-related quality of life measures [8]. Apart from the symptoms themselves, many patients struggle with anxiety. Relaxation therapy has been suggested to increase the quality of life in patients, according to a small clinical study that would, however, require large-scale validation [9].

While therapy for these diseases has come a long way, from allergen-specific immunotherapy purely symptomatic treatments such as antihistamines and modern biologics, management of allergic diseases still proves challenging due to variable adherence to long-term treatments and inconsistent response due to the multitude of existent pathological phenotypes. This is a testimony of the complex processes behind allergies, which still require more study, understanding, and systematization.

The allergic diseases affecting the airways—mainly allergic rhinitis, chronic rhinosinusitis with or without nasal polyps, and asthma—have been treated as different entities by medical practitioners. However, the similarities and the epidemiological association between them [10] have driven some to believe that these may actually be one disease since as early as 2001, when Professor Jean Bousquet authored the published article “Allergic rhinitis and its impact on asthma” [11]. However, while Jean Bousquet et al. have formally introduced this theory through the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, J. Grossman had published an article advocating for a similar hypothesis even earlier, in 1997, called “One airway, one disease” [12]. This theory was then tackled several times in the 2000s [13,14,15], sparking the curiosity of many researchers. The “united airway disease” concept has been stipulated, which sees upper and lower airways as one organ that is commonly comorbid.

However, despite its rising popularity, the model is not universally accepted, and important contradictions are found in the literature. Some researchers argue that the embryological, anatomical, and functional differences between the nasal (ectodermal-derived) and bronchial (endodermal-derived) epithelium challenge the notion of a unified pathophysiology [16]. Others bring arguments about the variability in treatment response, especially in non-type 2 inflammation cases, as evidence of distinct disease mechanisms [1,17,18]. Additionally, the supporting evidence for the “united airway disease” is potentially subject to selection bias, and large-scale longitudinal studies and randomized trials are still missing.

Unfortunately, there is no consensus regarding this topic. Seeing all cases of rhinitis and asthma as completely inseparable entities seems inadequate. However, there are times when seeing the larger picture and treating the two together might be beneficial.

2. Epidemiological Data

As previously stated, both diseases are currently widespread in the population. Certainly, many adults who suffer from mild symptoms of allergic rhinitis, for example, will overlook it as a simple cold or flu and will not consult a clinician in order to be adequately diagnosed. Also, it can be expected that these numbers will only rise in the future, as our lifestyle changes and adapts to the technological advancements and cultural changes.

However, the epidemiological data regarding both diseases present simultaneously is rather scarce. A review by Nappi et al. from 2022 has found that 80% of patients with asthma have allergic rhinitis and 30% of patients with allergic rhinitis have asthma, but this review does not present primary data and may reflect selection bias from included sources [10]. A large meta-analysis encompassing 29 studies and almost 300,000 patients has also found that patients with a history of allergic rhinitis are likely to develop asthma at some point in their life [19]. This conclusion is supported by consistent results across diverse populations, even though variability in study designs may limit generalizability.

This association seems to be beyond what could be considered coincidence. Also, while these studies refer to documented clinical cases, the real number of undiagnosed patients with this comorbidity may be significantly higher.

However, it must also be noted that not all cases of rhinitis have asthma, and not all asthma cases have rhinitis. While for some of the patients that only have one disease, it is only a matter of time until they develop the other, it is unlikely that all of them will do so. Certainly, there are numerous cases that suffer only from rhinitis or only from asthma for their entire life.

Surely enough, a comprehensive review that integrates epidemiological and clinical data that was published in 2023 has put out a similar hypothesis [1], which will be incorporated in the following paragraphs. However, further validation in the form of large-scale studies that eliminate selection bias is required to confirm this classification.

3. Pathology

In the past decade, the type 2 inflammation perpetuated by T helper 2 (Th2) lymphocytes was proven to be at the base of allergic rhinitis [20], present in most patients with asthma (but not all) [21], and in other allergic diseases such as chronic rhinosinusitis with or without nasal polyps (CRSwNP/CRSsNP), eosinophilic esophagitis, and atopic dermatitis [22]. What is more, a 2024 review of emerging immunological evidence and biomarker-driven phenotyping has suggested that even chronic obstructive pulmonary disease (COPD) may have an important type 2 inflammation component in about a third of patients [23], albeit through different cells than the ones found in asthma. It was previously believed that this subtype of inflammation has little importance in COPD. While the study builds on growing support for phenotypical and inflammatory heterogeneity in COPD, the clinical implications remain under investigation.

Type 2 inflammation has been a highlight of academic studies after the discovery of the immune cell subtypes, including the T helper (Th) lymphocytes—more exactly the Th2 subtype. While the Th2 cells may play an important role in this inflammation type, there are many other cells involved, including B cells (mainly type 2 B cells), NK cells, eosinophils, and macrophages [22]. It is not yet known which of these cells is the most important in the process. These cells respond to several stimuli, including proteins, parasites, viruses (specifically rhinovirus C for children and influenza A for adults and respiratory syncytial virus (RSV)), and bacteria (more precisely, Staphylococcus aureus, which seems to have a strong effect in adolescents) [1].

While this immune response’s main purpose may have originally been protection against parasites, the factors affecting modern humans have altered the balance between this system’s suppression and activation, causing it to be abnormally active and to play an important part in the aforementioned diseases. While viruses and bacteria do not directly activate this type of inflammation, they can alter the balance between the tissue cytokines involved in this response, causing an exaggerated activation, or they may harm the integrity of the mucosal layer, allowing other stimuli to pass in the deeper layers and reach the cells involved in the type 2 inflammation more easily (the skin barrier dysfunction theory [1]). Therefore, epithelial dysfunction (leading to “barrier leakiness” [22]) caused by a multitude of factors may play a role in asthma and allergic rhinitis, similar to the way endothelial dysfunction plays a role in atherosclerosis. However, a non-type 2 response can also be triggered by viral infections, causing an allergic reaction independent from the type 2 response. These infections cause oxidative stress, cell death, and mitochondrial dysfunction, which are currently under intense study, as measuring these processes may make for potentially useful biomarkers [5].

The main cytokines involved in the type 2 inflammation are the interleukins IL-4, IL-5, IL-9, IL-13, and IL-33 [1,22]. These are important for two reasons: firstly, they can be used as biomarkers to assess the gravity of the disease and the efficacy of the treatment, and secondly, they are the main targets of the current (and possibly future) biological treatment.

Some children may be born with abnormal Th2 signaling and have a predisposition to quickly develop several diseases associated with this immune response as they advance in age and come into contact with several aggravating factors. This process is known as “the atopic march” [1].

Therefore, asthma and rhinitis may have a common pathological pathway. What is more, while it has been known for a long time that viral intercurrences can destabilize and decompensate asthma (through the mechanism mentioned before), it seems that viral infections of the nose cavity are also able to kickstart an allergic rhinitis episode [5,24].

All these arguments seem to support the “united airway disease” theory. However, there are notable cases of rhinitis alone that are not related to the onset of asthma. These patients suffer from a strictly localized disease that has different pathological pathways involved. The main factors involved in rhinitis as a standalone, localized disease are Toll-like receptors (TLR) and IL-17. What is more, genes that are involved in allergic rhinitis and asthma together (17q12-21 and 11q13.5 loci, which contain several genes associated with these diseases) are not involved in the localized version of non-allergic rhinitis (which in turn has 27 genes contributing to the disease’s pathogenesis that are different from the previous ones; one such gene is myeloid differentiation primary response gene 88 (MyD88)) [1]. Neutrophils are also found in larger numbers in the nasal mucosa during allergy seasons in these patients, and eosinophils, while still present, are found in lower numbers than in patients with typical type 2 inflammation present [25]. These are very important differences that cannot be overlooked.

Dysbiosis also seems to play an important role in the development of allergic diseases, to the point where it may be used as a biomarker to assess the risk of a child becoming afflicted. This is true for both the airway microbiome and the intestinal microbiome. In the airway, an increase in the populations of Moraxella, Prevotella, Veilonella, and Gemella and a decrease in the populations of Corynebacterium and Dolosigranulum mark an increased risk of children under 1 year of age developing asthma later in life. Similarly, increased numbers of E. coli, Gemmiger, Candida, and Rhodotorula and a smaller number of Faecalibacterium, Lachnospira, Rothia, Bifidobacterium, Veilonella, and Akkermansia have a similar effect [5]. The exact mechanisms implicated in this process are not yet precisely known. However, it has been observed that a healthy microbiome maintains low levels of IL-17, which increases after a certain degree of dysbiosis is achieved. A further aggravation of the dysbiosis will also cause IL-33 levels to spike [1]. These changes, coupled with a genetic predisposition, increase the chances of the patient developing polysensitization and allergic diseases. A cross-sectional comparison of young individuals in Finnish and Russian Karelia (regions with contrasting allergy prevalence) performed in 2020 suggests that people who have a richer, more diverse microbiome have a higher innate response tolerance and are more resistant to allergen sensitization [26]. Another study performed on Amish and Hutterite populations has hypothesized that a more traditional and agricultural lifestyle, which promotes contact with a higher number of diverse bacteria, helps to shape the innate immune response and allows the human body to better differentiate harmful and harmless antigens [7]. This study employed genomic, immunologic, and environmental analyses to show important differences in the expression of immune genes and asthma prevalence between two genetically similar populations with differing lifestyles and cultures. All these considered, the scientific community is only starting to uncover the impact that the Western lifestyle and eating habits have on the microbiome, which in turn has an important influence on allergic pathogeny.

There are also types of asthma that have little to no relation to the type 2 inflammation explained before. These non-type 2 asthma phenotypes are not fully understood but seem to have a late onset and afflict patients who suffer from obesity, patients who are smoking, or those who have other psychological factors involved [5]. Higher than normal levels of neutrophils can be detected in sputum, which may signal some sort of subclinical infection of the lower respiratory tract. Also, non-type 2 cytokines may be involved, such as IL-17 and IL-8, which are also involved in non-allergic rhinitis. These arguments might hypothesize a connection between non-type 2 asthma and standalone rhinitis (similar to the connection between allergic rhinitis and asthma), seeing as neutrophils and non-type 2 interleukins appear to be involved in the pathogenesis of both.

4. Clinical Considerations

From a clinical point of view, there are several factors that may be of interest to medical practitioners. There seems to be a synergistic effect that the diseases have when present together. Therefore, patients with both allergic rhinitis and asthma will have stronger symptoms in both diseases, and managing them becomes more challenging. If CRSwNP is also present (

Table 1. Key features of type 2 inflammation and non-type 2 inflammation (Th2 cells—T helper type 2 lymphocyte cells; Th1 cells—T helper type 1 lymphocyte cells; ILC2s—Type 2 innate lymphoid cells; IL—interleukin; COPD—chronic obstructive pulmonary disease) [1,21,29,30,31,32,33,34,35].

	Type 2 Inflammation	Non Type 2 Inflammation
Cells involved	Eosinophils, Th2 cells, ILC2s, mast cells, basophils	Neutrophils, Th1 cells, macrophages
Cytokines involved	IL-4, IL-5, IL-9, IL-13, IL-33	IL-8, IL-17, Toll-like receptors
Onset of diseases	Mainly in childhood or early life	Mainly adult-onset related to environmental factors
Triggers	Allergens, parasites	Pollution, infections, smoke
IgE levels	High	Normal
Corticosteroid response	Responsive	Poorly responsive
Biologic therapy available	Omalizumab, Mepolizumab, Dupilumab, Tezepelumab	Unavailable (Tezepelumab?)
Clinical Phenotypes	Allergic asthma, allergic rhinitis	Neutrophilic asthma, non-allergic rhinitis
Common Comorbidities	Atopic dermatitis, food allergies, nasal polyps, eosinophilic esophagitis	Obesity, COPD (related to smoking), psychological factors

), alongside the NSAID-exacerbated respiratory disease (NERD), all of these diseases will be more difficult to treat and control. This association also bears the name of Widal syndrome [27] or Samter’s triad [28]. The polyps in this case will have an increased rate of corticosteroid dependence and recurrence, requiring more surgeries for removal. Asthmatic exacerbations will be present more often will be more difficult to manage, and aspirin and other NSAIDs can kickstart these exacerbations when administered.

The onset and multimorbidity of the pathological phenotypes also differ considerably. Children that become polysensitized from an earlier age have an increased risk to develop both rhinitis and asthma (within about a decade) [1]. They are also more sensitive to non-allergenic stimuli (such as the inhalation of cold air) as well as allergic stimuli, and a family history with allergies is more frequently found in these children [1].

On the contrary, patients suffering from rhinitis alone are usually sensitized to one or a few allergens, to which the sensitization is performed through the major histocompatibility complex (MHC) Class II allergen sensitization. These patients rarely have a family history, and the allergens most commonly involved are ragweed, pollen, and birch trees. Still, it is not impossible that these patients may become polysensitized later in life.

5. Benefits of Common Treatment

Up until recently, allergic diseases affecting different parts of the airway have been treated as separate entities (albeit with similar medication, such as corticosteroids) [36]. However, as the connections between these diseases have been further studied and understood, it has become clear that treating all respiratory pathology as a whole can have benefits. For example, the novel approach in controlling asthma in patients that suffer from CRSwNP is to treat the nasal polyps [36]. Whether this is performed through medication (corticosteroids, saline irrigations, or some antibiotics such as doxycycline) and then through surgery if needed, managing the asthma becomes easier [36].

As seen in the previous paragraphs, viral infections in particular seem to be able to cause imbalances in the epithelial homeostasis, which can exacerbate both type 2 and non-type 2 rhinitis and asthma. Periodical vaccination against some types of these viruses may prove useful in preventing these episodes by increasing the subject’s specific immunity.

Allergen immunotherapy (introduced in 1911 by Leonard Noon), whether it is administered sublingually or subcutaneously, to this day remains the only disease-modifying treatment option for immunoglobulin E (IgE)-mediated allergic diseases, especially allergic rhinitis and asthma, but also allergic rhinoconjunctivitis. It works by gradually inducing tolerance through systematic, controlled, and repeated exposure to specific allergens, ultimately reducing symptom severity and the need for symptomatic medication. A 2022 meta-analysis recently reconfirmed the long-term efficacy of allergen immunotherapy in controlling symptoms and preventing the progression from rhinitis to asthma in both children and adults [37]. However, despite its potential, this type of therapy has limitations such as long treatment duration (3–5 years in general), which in turn leads to variable patient adherence and response. The risks of adverse reactions, particularly anaphylactic shock, must also be taken into consideration. Moreover, its effectiveness is largely restricted to certain phenotypes of these diseases, particularly mono- or oligo-sensitized individuals with clearly identified allergen triggers (such as ragweed), which may limit its applicability in atopic, polysensitized patients or patients with non-allergic phenotypes [38]. Therefore, more data is needed for careful patient selection criteria and development of delivery models that would help increase treatment adherence.

Biological treatments are becoming increasingly more available for these diseases. Omalizumab, an anti-IgE monoclonal antibody, has been used in the treatment of asthma since 2003. However, as we have seen, the pathological pathways of these diseases are complex. More targeted therapies have been introduced, targeting key cytokines involved in the type 2 inflammation response. Mepolizumab inhibits IL-5, while dupilumab inhibits the IL-4 receptor alpha subunit and is effective on both the upper and the lower respiratory tract.

For those that suffer from the non-allergic variant of these diseases and mainly have a non-type 2 inflammatory response involved in the pathogenesis of their afflictions, biologics are yet to be introduced. There seems to be a gap in the literature regarding this subject, and a more thorough understanding is needed regarding the immunological, cytological, and pathological factors of these types of diseases. However, a recent notable case report brings promising perspectives in this regard [34]. An 80-year-old woman suffering from uncontrolled asthma, with low levels of eosinophils and fractional exhaled nitric oxide (FeNO) (which suggest a non-type 2 asthma), has been, over the years, treated constantly with high doses of triple therapy (ICS/LABA/LAMA) and bronchial thermoplasty. Attempts have also been made to manage the asthma with Benralizumab, Dupilumab, and Mepolizumab. However, all these seemed to fail, and the asthma remained uncontrolled. A novel molecule was then used, Tezepelumab, which is a thymic stromal lymphopoietin (TSLP) inhibitor. TSLP is the first cytokine involved in the recruitment of effector cells in asthma, including eosinophils, basophils, Th2 lymphocytes, and also neutrophils. By blocking this cytokine, the entirety of the pathological pathway seems to be interrupted. In this patient, the asthma control test (ACT) has been improved, and control of the severe asthma has been obtained. The NAVIGATOR study [35], a randomized, phase 3, double-blind trial, has also suggested the efficacy of Tezepelumab in non-type 2 severe asthma. While highly rigorous, the underrepresentation of this subgroup of patients in the study would require more large-scale evidence for further validation. Another interesting perspective would be the assessment of Tezepelumab’s efficacy in the management of non-allergic, standalone rhinitis.

Promising data is currently being uncovered regarding the prevention of allergic diseases. Early allergen introduction (the LEAP study [39]), maternal breastfeeding [40], and the “hygiene hypothesis” [41] (and its role in dysbiosis—which has also been tackled in this review) have all been suggested to help prevent the development of allergies. However, more data is required in order to create a clear set of guidelines to be put at the disposal of parents in order for them to help prevent the occurrence of allergic diseases in future generations.

Summing up, the main points supporting the United Airway Disease concept have been summarized in the figure presented below (Figure 1), while the main points contradicting this concept have been presented in the introduction.

6. Discussions

The reader should be aware that this field remains filled with many unknowns, though it is undoubtedly a promising area of research. The main limitation of this review is its reliance on a relatively small number of published works, which introduces the possibility of selection bias. Unlike systematic reviews, it does not follow a defined literature search protocol and includes a range of heterogeneous studies, which limits comparability. Additionally, this narrative review is constrained by a lack of thoroughly documented real-world data. Lastly, it is not exhaustive of the topic and may be limited in terms of scientific novelty.

There are novel articles that tackle very particular aspects of this topic. For example, a 2025 review [42] has recently analyzed the importance of IL-8 in the pathogenesis of allergic rhinitis and CRSwNP. While other interleukins such as IL-4 and IL-13 have an established and proven role, the newest theories are that IL-8, which is a chemotactic cytokine involved in the recruitment of neutrophils in the inflamed tissues, may also play a part in the process. IL-8 has reportedly been discovered in high levels in patients who suffer from these types of rhinitis. As mentioned before, the role of neutrophils in rhinitis has been observed in the past. Future studies on this matter (i.e., a large cohort study with three patient groups [42]) may shed more light on the importance of IL-8 and, subsequently, neutrophils in these diseases. Moreover, the role of IL-8 may perhaps extend to asthma as well, as we have seen that non-type 2 asthma is characterized by an increased number of neutrophils in the sputum.

Another review from 2023 analyzes the importance of the biological treatment in patients with chronic rhinosinusitis [43]. This review highlights current evidence supporting the use of biological compounds in select patients with severe, type 2 inflammation-driven disease. It emphasizes the potential of these targeted therapies to improve symptom control and reduce the need for surgery, though it is challenged by the necessity for more long-term, large-scale data in this subgroup of patients.

One matter stands out: biological treatment can only be initialized in patients if they meet a number of criteria, one of which is comorbid asthma and another one is the presence of type-2 inflammation. Given these criteria, it is clear that more and more ENT practitioners are becoming aware of the strong association between the nasal pathology and the pulmonary one and the benefits of synergic treatment. Pulmonologists worldwide should also follow suit and closely conduct anamnesis in their asthma patients in order to detect possible nasal symptomatology and work alongside their ENT peers in order to treat these patients of both manifestations.

Potential fields of further study are: the importance of IL-8 in asthma; non-allergic rhinitis; neutrophilic/non type-2 asthma; importance of neutrophils in the pathogenesis of rhinitis and asthma; etiopathogenesis correlation between respiratory allergies, food allergies and skin allergies; role of viral infections in the exacerbation of allergic rhinitis and asthma together; the importance of the different embryogenic origins of nasal epithelia (derived from the ectoderm) and lung epithelia (derived from the endoderm) in the “united airway disease” concept; the efficacy of Tezepelumab in patients with non-allergic rhinitis and neutrophilic asthma; methods of prevention for allergic diseases.

7. Conclusions

This review is a mere glimpse of the hidden complexity and connections of what may seem to be two completely different diseases. There are striking similarities in the epidemiology and pathology of these diseases, which in turn have a large impact on the clinical manifestations that the patient suffers. Common treatment for both pathologies is beneficial and desirable. Potential prevention methods should also be explored, and a clear set of recommendations should be established.

All things considered, there are situations in which seeing rhinitis and asthma as one disease that affects different parts of the respiratory system is justified and beneficial for the patient.

However, there are also situations in which rhinitis can act as a standalone disease with different genes and pathological pathways involved and cases where type 2 inflammation plays little to no part in the development of asthma. The embryonical, anatomical, and functional differences between the nose and the lung are also significant, and the literature still lacks the evidence needed to reach a consensus. Certainly, a simplified, one-fits-all approach is therefore not possible, but that shouldn’t stop practitioners from always being up to date with the latest developments and seeking to team up and analyze cases through a multidisciplinary approach, in the best interest of the patient.