Abstract
Asthma and allergic rhinitis are common health problems that cause major illness and disability worldwide. The prevalence of allergic rhinitis is estimated to range from 10% to 20% in the USA and Europe. Multiple factors contribute to the wide range of reported prevalence rates. These include type of prevalence rate reported (current or cumulative), study selection criteria, age of participants, differences in survey methods, varied geographic locations and socioeconomic status, any of which are significant enough to confound direct comparison between studies. There is no standard set of diagnostic criteria for allergic rhinitis. In most studies, the criteria for diagnosis are based on the subject’s reporting, solely by questionnaire and rarely confirmed by skin testing. In addition, most studies focus on hay fever, leaving perennial allergic rhinitis underestimated. Sinus imaging is generally not performed and, therefore, rhinosinusitis not differentiated. Some investigators report ‘current’ prevalence while others report ‘cumulative’ or ‘lifetime’ prevalence. Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. The prevalence of asthma is <2% in subjects without rhinitis while it varies from 10% to 40% in patients with rhinitis. Furthermore, the majority of patients with asthma experience rhinitis, which is a factor in the risk for asthma. Despite recognition that allergic rhinitis and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. This aim of this review is to enable the reader to discuss prevalence, risk factors and prognosis of allergic rhinitis and asthma.
Keywords
Introduction
Asthma and allergic rhinitis (AR) are common health problems that cause major illness and disability worldwide. Several studies have shown that rates for asthma vary considerably from one country to another and there are more than 300 million people worldwide who are affected by asthma [Bousquet et al. 2008; Masoli et al. 2004]. The prevalence of AR is estimated to range from 10% to 20% in the USA, UK, Germany, Switzerland and Finland [Masoli et al. 2004; Bauchau and Durham, 2004; Von Hertzen and Haahtela, 2005]. Using a conservative estimate, it is proposed that AR occurs in approximately 500 million people. About 200 million people also have asthma as a comorbidity.
Despite recognition that AR and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. Reports spanning the last few decades indicate that the prevalence of AR and asthma appears to be increasing [Lundback, 1998; Linneberg et al. 2000, 2001; Riedi et al. 2005]. This aim of this review is to enable the reader to discuss prevalence, risk factors and prognosis of AR and asthma.
Definition of allergic rhinitis
The clinical definition of rhinitis is difficult to use in the epidemiologic settings of large populations where it is impossible to visit everybody individually or to obtain the laboratory evidence of each immune response. The standardization of the definition of rhinitis in epidemiologic studies is of crucial importance. However, many patients poorly perceive nasal symptoms of AR: some exaggerate symptoms, whereas many others tend to dismiss the disease [Zacharasiewicz et al. 2003]. Moreover, a large proportion of rhinitis symptoms are not of allergic origin. In fact, knowledge of patients’ perceptions of AR and its consequences are scarce. Patients with AR usually experience significant emotional burden and restrictions to daily life. They mostly share satisfaction with the current treatment options and dissatisfaction with most of the preventive measures. While being satisfied with medical treatment, patients suffer a significant impact in daily life.
AR is defined as an immunologic response modulated by immunoglobulin E (Ig E) and characterized by sneezing, rhinorrhea, nasal congestion and pruritus of the nose. Postnasal drip mainly occurs. Preschool children may just have nasal obstruction. AR can be classified as seasonal (commonly called hay fever), which most frequently results from IgE-mediated sensitivity to pollen allergens (tree, grass, or weed). Alternatively, AR can be classified as perennial, most commonly caused by allergy to animal dander or dust mites [International Rhinitis Management Working Group, 1994; Dykewicz and Fineman, 1998; Van Cauwenberge et al. 2000]. Recently, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have proposed a new classification scheme, which proposes that the ‘seasonal/perennial’ classification be replaced by ‘intermittent/persistent’. Objective tests for the diagnosis of IgE-mediated allergy can also be used [Droste et al. 1996]. The diagnostic efficiency of IgE, skin prick tests and Phadiatop® was estimated in 8329 randomized adults from the SAPALDIA. The skin prick test had the best positive predictive value (48.7%) for the epidemiologic diagnosis of AR compared with the Phadiatop® (43.5%) or total serum IgE (31.6%) [Tschopp et al. 1998].
The severity of AR can be classified as ‘mild’ or ‘moderate/severe’ [Bousquet et al. 2008]. AR is characterized by subjective symptoms which may be difficult to quantify due to the fact that they depend largely on the patient’s perception. Patients usually suffer from sleep disorders and emotional problems, as well as from impairment in activities and social functioning [Leynaert et al. 2000a]. Moreover, H1-antihistamines with sedative properties can increase sedation in patients with AR [Casale et al. 2003]. It is also commonly accepted that AR impairs work [Blanc et al. 2001] and school performance [Blaiss, 2004]. In several studies, the severity of AR, assessed using quality of life (QOL) measures, work productivity questionnaires or sleep questionnaires, was found to be somewhat independent of duration [Leger et al. 2006; Szeinbach et al. 2007]. Objective measures of the severity of allergic rhinitis include: symptom scores; visual analog scales (VASs); measurements of nasal obstruction using peak inspiratory flow measurements, acoustic rhinometry and rhinomanometry [Clement and Gordts, 2005; Starling-Schwanz et al. 2005]; measurements of inflammation by nitric oxide levels, cells and mediators in nasal lavages, cytology and nasal biopsy [Ragab et al. 2006; Struben et al. 2006]; reactivity measurements such as provocation with histamine, methacholine, allergen, hypertonic saline, capsaicin, or cold dry air [Litvyakova and Baraniuk, 2001]; measurements of the sense of smell [Moll et al. 1998]. Measurements of VASs, nasal obstruction and smell are used in clinical practice. The VAS has been validated for the assessment of rhinitis severity graded according to ARIA [Bousquet et al. 2008]. The other measurements are primarily used in research.
Prevalence studies
The nasal airways and the closely associated paranasal sinuses are an integral part of the respiratory tract. The nasal and bronchial mucosa present similarities and one of the most important concepts regarding nose–lung interactions is the functional complementarity. Most patients with asthma have rhinitis suggesting the concept of ‘one airway one disease’ [Bousquet et al. 2003]. The presence of AR commonly exacerbates asthma, increasing the risk of asthma attacks, emergency visits and hospitalizations for asthma. However, not all patients with rhinitis have asthma and there are differences between rhinitis and asthma [Bousquet et al. 2004; Bachert et al. 2004].
Despite recognition that AR and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. Many national or multinational studies are rapidly improving our knowledge in the prevalence of rhinitis and its possible risk factors. These include:
the second National Health and Nutrition Examination Survey [Turkeltaub and Gergen, 1991; Gergen and Turkeltaub, 1992];
the ECRHS [European Community Respiratory Health Survey, 1996];
the International Study on Asthma and Allergy in Childhood (ISAAC I) [Strachan et al. 1997] and its follow-up study (ISAAC III) [Mitchell et al. 2009];
the SAPALDIA [Wuthrich et al. 1995]
the Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution, Climate and Pollen (SCARPOL) [Braun-Fahrlander et al. 1999].
The clinical definition of rhinitis is difficult to use in the epidemiologic settings of large populations where it is impossible to visit everybody individually or to obtain the laboratory evidence of each immune response. It seems that there is an overestimation of AR using questionnaires only and that the attributable fraction of IgE-mediated allergy in patients with a diagnosis of AR by questionnaires is slightly over 50% [Arshad et al. 2002]. Thus, studies using questionnaires only may overestimate the true prevalence of AR.
The prevalence of seasonal AR using questionnaires ranges from 1% to 40% (Table 1). The prevalence of perennial rhinitis varies from 1% to 13%. The prevalence of seasonal AR is higher in children and adolescents than in adults. Perennial rhinitis is more common in adults than in children but few reliable data exist [Jessen and Malm, 1997]. In the Tucson study, it was found that 42% of children had doctor-diagnosed rhinitis at 6 years of age [Wright et al. 1994]. In more recent studies, the prevalence of AR has increased, in particular in countries with low prevalence [Falade et al. 2004; Asher et al. 2001; Akcakaya et al. 2000; Shamssain and Shamsian, 2001].
Cumulative prevalence of allergic rhinitis in monocentric epidemiologic surveys
In a study on the general population in Europe, the prevalence of AR was found to be around 25% [Bauchau and Durham, 2004, 2005]. The prevalence of confirmable AR in adults in Europe ranged from 17% (Italy) to 28.5% (Belgium); see Table 2. The ECRHS was set up to answer specific questions about the distribution of asthma and the health care given for asthma in the European Community [Burney et al. 1994]. The ISAAC design comprises three phases [Asher et al. 1995; Asher and Weiland, 1998; Braun-Fahrlander
Prevalence of allergic rhinitis in the general population.
Factors affecting the prevalence of allergic rhinitis and asthma
Multiple factors contribute to the wide range of reported prevalence rates of AR. These include type of prevalence rate reported (current or cumulative), study selection criteria, age of participants, differences in survey methods, varied geographic locations and socioeconomic status, any of which are significant enough to confound direct comparison between studies. There is no standard set of diagnostic criteria for AR. In most studies, the criteria for diagnosis are based on the subject’s reporting, solely by questionnaire and rarely confirmed by skin testing. In addition, most studies focus on hay fever, leaving perennial allergic rhinitis underestimated. Sinus imaging is generally not performed and, therefore, rhinosinusitis not differentiated. Some investigators report ‘current’ prevalence rate, which refers to the percentage of the population with the condition during the previous 12 months. Other authors report ‘cumulative’ or ‘lifetime’ prevalence, which is the percentage of a population who have ever had the condition at any time during their life.
Rural–urban differences and modification of life style
Studies in central America [Soto-Quiros et al. 2002], Europe [Von-Mutius et al. 1994] and South Africa [Crockett et al. 1995] have shown that the prevalence of AR is higher in urban than in rural areas [Nicolaou et al. 2005]. This is particularly the case for pollinosis, whereas pollen counts are usually higher in urban than in rural areas. The children of farmers have less AR than other children, suggesting that a countryside lifestyle could possibly protect children from the development of allergy [Leynaert et al. 2001; Kilpelainen et al. 2002; Wickens et al. 2002; Braun-Fahrlander, 2003]. The ‘protective’ farm effect was related to livestock farming and thus to microbial exposure. A dose-dependent inverse relationship between the exposure to endotoxin in the mattress dust of children and the occurrence of atopic diseases was shown in rural environments [Braun-Fahrlander et al. 2002]. Another possible protective mechanism is the ingestion of nonpasteurized milk in infancy [Perkin and Strachan, 2006]. Asthma and allergic diseases in developing countries are associated with the adoption of an urbanized lifestyle. In 1989, in East German children, there was a reduced prevalence of atopy and seasonal AR in comparison with West German children [Von-Mutius et al. 1994]. Similar trends have been observed in the Baltic States and Scandinavia [Braback et al. 1994] or between Finland and Russia [Dotterud et al. 2000]. Although there is some controversy, it seems that the prevalence rate of atopy and seasonal AR is now similar in all parts of Germany [Von-Mutius et al. 1998]. However, in some former Eastern European countries such as Estonia, the prevalence of allergy does not appear to increase due to a change in lifestyle [Annus et al. 2005].
Infections in the neonatal period
The negative association between atopy and number of siblings agrees with earlier reports [Braback et al. 1995]. However, when it comes to the various aspects of family size (older and younger siblings, brothers and sisters) the literature gives inconsistent conclusions. Several papers show a stronger effect of older siblings compared with younger siblings, whereas in one study Strachan and colleagues could find no such difference [Strachan et al. 1996, 1997]. Jarvis and colleagues found a stronger effect of family size than of birth order in a subset of the ECRHS [Jarvis et al. 1997].
The hygiene hypothesis
Strachan first proposed that infections and unhygienic contact might confer protection against the development of allergy [Strachan, 1989]. The hygiene hypothesis suggests that an early-life environment primes the immune system in the Th1 direction (nonallergic) while a ‘sterile’ environment tends to promote the development of allergy. Although mechanisms related to Th1/Th2 balance undoubtedly are of primordial importance for the development of allergies, they might not suffice to explain the effects related to the hygiene hypothesis. Mechanisms operative at other steps of allergy development have to be considered when trying to understand the effects of microbial exposures. Serum levels of IgE, as of any other Ig isotypes, are not only determined by means of class-switch recombination to this isotype but also by factors regulating terminal differentiation of already switched B cells and the rate of secretion of IgE. IL-6, a proinflammatory cytokine, is one prominent factor governing these processes. Furthermore, T regulatory cells, in interaction with dendritic cells, occupy a central role in controlling immune responses and their importance for the development of allergies has been well documented. Finally, mechanisms inherent to the innate immune system related to endotoxin tolerance can also contribute to the effects elicited by exposure to microbes.
Immunization
An inverse association between tuberculin responses and atopy was observed in Japanese children [Shirakawa et al. 1997], indicating that BCG immunization, subclinical exposure to
Other factors
Changes in lifestyle. A restrictive use of antibiotics and vaccinations and a diet containing live lactobacilli, appears to prevent the development of allergy [Alm et al. 1999].
Obesity may increase the prevalence or the severity of symptoms in patients with allergic rhinitis, but more data are needed [Kilpelainen et al. 2006; Radon and Schulze, 2006].
Increase in exposure to allergen, pollution and irritants (smoke, gas) [Korsgaard and Iversen, 1991; Davies et al. 1998]. Studies on the relationship between allergy in parents and allergy in their children should always consider the home environment as a potential confounder.
The link between physical activity, allergic diseases and asthma needs to be investigated in more detail [Platts-Mills et al. 2006].
Stress.
Prevalence of asthma in patients with rhinitis
Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients [Bousquet et al. 2008]. The prevalence of asthma in subjects without rhinitis is usually <2%. The prevalence of asthma in patients with rhinitis varies from 10% to 40% depending on the study [Bousquet et al. 2005; Linneberg et al. 2002; Leynaert et al. 2004; Downie et al. 2004]. Patients with a sensitization to indoor and outdoor allergens are more prone to have asthma as a comorbidity than those with indoor or outdoor allergy [Leynaert et al. 2004]. Although all patients with rhinitis may suffer from asthma [Antonicelli et al. 2007], patients with moderate/severe Persistent Allergic Rhinitis (PAR) may be more likely to suffer from asthma than those with Intermittent Allergic Rhinitis (IAR) and/or a milder form of the disease [Bousquet et al. 2005]. Mucosal swelling was found to be common in asthmatics [Hellgren et al. 2002]. The difference between rhinitis patients with or without asthma symptoms may be partly related to the perception of dyspnea in patients with bronchial hyperreactivity [Aronsson et al. 2005].
Prevalence of rhinitis in patients with asthma
The majority of patients with asthma experience rhinitis symptoms [Linneberg et al. 2002; Sakar et al. 2006]. However, in many instances, symptoms may predominate in one organ and be hidden or unrecognized in other organs even though they exist. In preschool children, nasal symptoms and wheezing may present a different relationship than later in life [Viegi and La Grutta, 2007].
Rhinitis is a factor independent of allergy in the risk for asthma [Leynaert et al. 2000b]. However, the results observed in some developing countries may differ from those in Western populations [Celedon et al. 2001; Mavale-Manuel et al. 2007; Ait-Khaled et al. 2007]. In these countries, rhinitis and asthma may be independent. However, the prevalence of rhinitis and asthma in rural communities or low-income countries is generally lower than in developed Westernized urban communities. A considerable difference between the prevalence of symptoms and the prevalence of medical diagnosis detected in underserved populations may suggest a significant proportion of underdiagnosis, which might be related to a lack of awareness and limited access to health care [Hailu et al. 2003]. In other developing countries such as Vietnam [Nga et al. 2003], Nigeria [Falade et al. 1998], Bangladesh [Kabir et al. 2005] or Brazil [Sole et al. 2004], childhood atopy symptom prevalence and links between rhinitis and asthma are similar to those in developed countries.
Recently, Braido and colleagues stated that control of rhinitis in asthma patients can lead to an optimization of QOL related to the upper airways, while this phenomenon is not so evident in asthma. They concluded that asthma patients must be evaluated for rhinitis and
Changes in the prevalence of asthma and rhinitis
Several studies have examined the changes in the prevalence of asthma and rhinitis in the same population using identical methods. Results are variable. The ISAAC was repeated for at least 5 years after phase I to examine the changes in the prevalence of the symptoms of these disorders [Mitchell et al. 2009]. A rise in the prevalence of symptoms was found in many centers, but an absence of increase in the prevalence of asthma symptoms in the older age group was observed for centers with an existing high prevalence.
Some studies have demonstrated a parallel increasing prevalence of asthma and rhinitis [Braback et al. 2004], whereas others have not. Often, it is found that rhinitis prevalence increases faster than asthma prevalence, which was also found to decrease in some countries [Huurre et al. 2004; Robertson et al. 2004; Vellinga et al. 2005]. It appears that in regions of highest prevalence, the proportion of subjects suffering from asthma or rhinitis may be reaching a plateau [Robertson et al. 2004].
The results of four consecutive surveys suggest that the increase in the prevalence of asthma and hay fever in 5- to 7-year-old children living in Switzerland may have ceased. However, symptoms of atopic dermatitis may still be on the rise, especially among girls [Grize et al. 2006; Braun-Fahrlander
These studies appear to indicate that the changes in the prevalence of rhinitis and asthma differ but they were not designed to show the variation in the links between the two sites of the airways.
Allergic rhinitis as a risk factor for asthma
The age of onset of atopy may be an important confounding factor for the development of asthma and rhinitis or rhinitis alone. In infants and very young children, lower respiratory tract symptoms often develop before nasal symptoms [Kulig et al. 2000]. It is difficult to make a clear diagnosis of asthma in this age group. In an Australian study, it was found that atopy acquired at an early age (before the age of 6 years) is an important predictive factor for asthma continuing into late childhood, whereas atopy acquired later was only strongly associated with seasonal AR [Peat et al. 1990].
Asthma develops more commonly in patients with rhinitis than in those without. The Children’s Respiratory Study showed that the presence of doctor-diagnosed AR in infancy was independently associated with a doubling of the risk of developing asthma by 11 years of age. In children and adults, AR as a risk factor for asthma was shown in a 23-year follow up of college students [Settipane and Settipane, 2000]. Significantly more (10.5%) of the students originally diagnosed with AR went on to develop asthma compared with 3.6% of those who did not have rhinitis. This study was confirmed by other studies [Plaschke et al. 2000; Guerra et al. 2002; Toren et al. 2002]. In both studies, the onset of asthma was associated with AR and in the US study, after stratification, rhinitis increased the risk of the development of asthma by about three times among both atopic and nonatopic patients and by more than five times among patients in the highest IgE tertile. Patients with rhinitis, with PAR and severe nasal symptoms and with a personal history of doctor-confirmed sinusitis had an additional increased risk of asthma development. The authors concluded that rhinitis is a significant risk factor for adult-onset asthma in both atopic and nonatopic subjects.
It is not clear whether AR represents an earlier clinical manifestation of allergic disease in atopic subjects who will later go on to develop asthma or whether the nasal disease itself is causative for asthma.
Conclusions
The nasal airways and their closely associated paranasal sinuses are an integral part of the respiratory tract. Most patients with asthma have rhinitis suggesting the concept of ‘one airway one disease’. The presence of AR commonly exacerbates asthma, increasing the risk of asthma attacks, emergency visits and hospitalizations for asthma. Using questionnaires, the prevalence of seasonal AR ranges from 1% to 40% and the prevalence of perennial rhinitis varies from 1% to 13%. Multiple factors contribute to the wide range of reported prevalence rates of AR. Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. The prevalence of asthma varies from 10% to 40% in patients with rhinitis and the majority of patients with asthma experience rhinitis. Despite recognition that AR and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history.
Footnotes
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
The authors do not have a financial relationship with any organization or company, nor has the research been sponsored by any commercial organization.