Allergic rhinitis (AR) and allergic asthma are two common allergic diseases. The prevalence of AR worldwide, including Thailand, is 20%-40% [1, 2]. Epidemiologic studies have shown that the prevalence of asthma in patients with AR is 19%-35%, which is higher than the prevalence of asthma in the normal population [3, 4].
There are various ideas about the linkage of upper and lower airways, such as sharing similar airway epithelial lining and pathophysiology, and both conditions respond to same treatment modalities [5-7]. AR may lead to the development of asthma or aggravate an asthmatic attack. The first hypothesis is nasobronchial reflex. This reflex is considered to arise because of evidence that nasal irritation can lead to bronchoconstriction [8]. The second hypothesis is that mouth breathing as a result of AR can lead to unconditioned (cold, dry) air that passes to the lower airway, resulting in bronchial hyperactivity [4]. The third hypothesis is related to the systemic inflammation after the local nasal allergy. Allergic inflammation in the nose leads to release of cytokines and mediators especially interleukin (IL)-5 from bone marrow [9]. The fourth hypothesis is chronic irritation of lower airway from postnasal drip [9].
To evaluate the lower airway function, spirometry is the standard test. There are various studies from the west that have studied the prevalence of spirometric abnormalities in AR without asthmatic symptoms [10, 11]. Force expiratory volume in 1 s (FEV1) and the forced expiratory flow between 25% and 75% of forced vital capacity (FEF25_75) have been proposed as early predictors of small airway hyperresponsiveness [11]. In those studies, the risk factors, such as age, sex, duration of symptoms, type of allergen sensitization and symptom severity have been shown to affect spirometric impairment in patients with AR.
In Thailand, the prevalence of asthma associated with ARmostly derives from history taking, implying that patients already have symptoms of asthma [12]. There are limited data of impaired spirometry in AR without asthma in Asians. Although there are several articles showing the relationship between AR and the lower airway, the majority describe AR with concurrent asthma or with aggravation/worsening of asthma symptoms [12-15]. Because of the different types of allergens (e.g. grass pollens) and different clinical manifestations of AR (e.g. seasonal vs. perennial), the objective of this study was to determine the prevalence and risk factors of abnormal spirometry in Thais with AR without lower airway symptoms.
The present study was a cross-sectional examination of pulmonary function in patients with AR The study was approved by the institutional review board of Siriraj hospital (certificate of approval No. Si224/2009). Written informed consent was obtained from all study participants. Patients with chronic (symptoms >1 year) rhinitis with positive allergic skin prick test (SPT) relevant to the history, 20-60 years old, and normal X-ray of the paranasal sinuses and the chest were included. SPT of common indoor allergens (house dust mite, cat, dog, and cockroach) and outdoor allergens (pollens and molds) was conducted. Once a diagnosis of AR was made, the severity of AR was classified according to the standard recommendations of the Allergic Rhinitis with its Impact on Asthma (ARIA) guidelines [16]. Exclusion criteria were pulmonary disease, asthma, current or previous smoking, severe cardiovascular disease, current use of ß-blocker drugs, pregnancy, aneurysm in the chest, aorta, or brain, previous history of ophthalmologic, abdominal or thoracic surgeries, immunodeficiency, hepatitis, and gastroesophageal reflux (by history).
Spirometry was performed using a computer assisted spirometer (Koko Spirometer, Ferraris Respiratory, Louisville, CO, USA). Patients stopped medication that may affect the spirometrie result before performing the test. The test was conducted by a single technician who is familiar with the technique recommended by the standard guidelines [17]. Two main values of spirometry including FEV and reversible airflow obstruction were considered. Airflow obstruction was defined as FEV1 values <80% of predicted [17, 18]. According to the guidelines, reversible airflow obstruction was defined as the increased FEV1 ≥12% from baseline [19]. The association between each spirometrie variable and AR parameters such as duration, severity, type of allergen sensitization were analyzed. The other variable of spirometry i.e. the force expiratory flow during 25-75 second (FEF25 75), was also recorded and analyzed because some articles proposed this value as a predictor of early airway obstruction [20-22].
Data were analyzed using STATA software (STATA version 12.0, Stata Corp, College Station, TX, USA). Age of subjects was shown in mean ± standard deviation (SD). Other baseline characteristic data including sex, duration of rhinitis symptoms, and type of allergen sensitization are expressed in number or percent.
Logistic regression analysis between spirometry and each variable/baseline parameter was analyzed.
We included 153 patients with AR in the present study. All patient participants fulfilled the criteria of symptoms of chronic rhinitis for one-year or more. None of them had any symptoms of asthma. Their characteristics are described in
The mean ± SD of FEV1 and FEF25–75 was 98.89 ±11.93 and 95.64 ± 22.42, respectively. Twenty-three cases (15%) had abnormal FEV1
Patient characteristics
Characteristics | Number (percent) |
---|---|
Age (years) | |
Mean ± standard deviation | 34.4 ±10.5 (range 20-59) |
Sex | |
Male/Female | 46 (30%)/107 (70%) |
Duration of symptoms | |
≤ 5 years | 62 (41%) |
5-10 years | 52 (34%) |
≥ 10 years | 39 (26%) |
Severity of allergic rhinitis | |
Mild intermittent | 38 (25%) |
Moderate/severe intermittent | 37 (24%) |
Mild persistent | 19 (12%) |
Moderate/severe persistent | 59 (39%) |
Allergic to indoor allergens | 25 (16%) |
Allergic to outdoors allergens | 16 (11%) |
Allergic to both indoor and outdoor allergens | 112 (73%) |
Prevalence of abnormal pulmonary function test results
Number (percent) | |
---|---|
Abnormal FEV1 | 23 (15%) |
Abnormal % change of FEV1 | 4 (3%) |
Abnormal FEF25–75 | 37 (24%) |
FEV1= Force expiratory volume in 1 second, FEF25–75 = force expiratory flow during 25-75 s
In 23 patients who had FEV1 less than 80% of predicted value, half had moderate to severe persistent symptom severity. The majority were sensitized to both indoor and outdoor allergens
Prevalence of abnormal pulmonary function (Force expiratory volume in 1 s <80%), duration of allergy, severity of allergic symptoms, and sensitization to allergens
Number | Prevalence (%) | |
---|---|---|
Overall prevalence | 153 | 23 (15) |
Duration of allergy | ||
≤ 5 years | 62 | 10 (16) |
5-10 years | 52 | 7 (14) |
≥ 10 years | 39 | 6 (15) |
Severity of allergic symptoms | ||
Mild intermittent | 38 | 4 (11) |
Moderate/severe intermittent | 37 | 5 (14) |
Mild persistent | 19 | 2 (11) |
Moderate/severe persistent | 59 | 12 (20) |
Sensitization to indoor allergens | 25 | 1 (4) |
Sensitization to outdoor allergens | 16 | 1 (6) |
Sensitization to both indoor and outdoor allergens | 112 | 21 (19) |
The sensitization to both groups of allergens was significantly associated with FEV1 abnormality (odds ratio = 7.79, 95%confidence interval (CI) 1.08-55.91,
Clinical characteristics and their relation to FEV1
Characteristics | Total | Subject with FEV1 < 80% | OR | 95%CI | |
---|---|---|---|---|---|
Duration of allergy (y) | |||||
≤ 5 | 62 | 10 (16%) | 1 | - | |
5-10 | 52 | 7 (14%) | 0.83 | 0.34-2.04 | 0.691 |
≥ 10 | 39 | 6 (15%) | 0.95 | 0.38-2.42 | 0.921 |
Severity of allergic symptoms | - | ||||
Mild intermittent | 38 | 4 (11%) | 1 | - | |
Moderate/severe intermittent | 37 | 5 (14%) | 1.28 | 0.37-4.41 | 0.691 |
Mild persistent | 19 | 2 (11%) | 1 | 0.20-4.98 | 1.000 |
Moderate/severe persistent | 59 | 12 (20%) | 1.93 | 0.67-5.55 | 0.203 |
Sensitization to indoor allergens | 59 | 1 (4%) | 0.23 | 0.08-1.65 | 0.09 |
Sensitization to outdoor allergens | 16 | 1 (6%) | 0.39 | 0.06-2.69 | 0.29 |
Sensitization to indoor and outdoor allergens | 112 | 21 (19%) | 7.79 | 1.08-55.91 |
OR = odds ratio, CI = confidence interval, FEV1= force expiratory volume in 1 s
Four patients had the percent changes of FEV1 ≥12% after bronchodilator administration. There was no association between abnormal percent change of FEV1 and the duration of allergy, symptom severity, type of allergen sensitization
Clinical characteristics and their relation to percent changes of FEV1
Characteristics | Total | Subject with percent change FEV1≥ 12% | OR | 95%CI | |
---|---|---|---|---|---|
Duration of allergy (y) | |||||
≤ 5 | 62 | 0 (0%) | - | - | |
5-10 | 52 | 3 (5.8%) | - | - | 0.06 |
≥ 10 | 39 | 1 (2.6%) | - | - | 0.21 |
Severity of allergic symptoms | |||||
Mild intermittent | 38 | 1 (2.63%) | 1 | - | |
Moderate/severe intermittent | 37 | 1 (2.7%) | 1.03 | 0.07-15.82 | 0.99 |
Mild persistent | 19 | 0 (0%) | 0 | - | 0.48 |
Moderate/severe persistent | 59 | 2 (3.39%) | 1.28 | 0.12-13.71 | 0.83 |
Sensitization to indoor allergens | 25 | 2 (8%) | 5.12 | 0.75-34.66 | 0.06 |
Sensitization to outdoor allergens | 16 | 0 (0%) | 0 | 0 | 0.48 |
Sensitization to indoor and outdoor allergens | 112 | 2 (1.79%) | 0.36 | 0.05-2.51 | 0.28 |
OR = Odds ratio, CI = Confidence interval, FEV1= force expiratory volume in 1 s
Thirty-seven patients had the value of FEF25–75 <80% of predicted value. From the univariate analysis, moderate/severe intermittent symptom severity seemed to affect FEF25–75. Therefore, in the multivariate analysis of symptom severity was not significant.
The duration of allergic symptoms >10 y significantly affected FEF25–75. Multivariate analysis found duration significantly affected FEF25–75 (adjusted OR = 2.07; 95%CI = 1.01-4.25,
Clinical characteristics and their relation to FEF25–75
Characteristics | Total | Participant with FEF2–75<80% | OR | 95%CI | |
---|---|---|---|---|---|
Duration of allergy (y) | |||||
≤ 5 | 62 | 10 (16%) | 1 | - | |
5-10 | 52 | 14 (27%) | 1.67 | 0.81-3.04 | 0.16 |
≥ 10 | 39 | 13 (33%) | 2.07 | 1.01-4.25 | |
Severity of allergic symptoms | |||||
Mild intermittent | 38 | 10 (26%) | 1 | - | |
Moderate/severe intermittent | 37 | 9 (24%) | 0.92 | 0.42-2.01 | 0.04 |
Mild persistent | 19 | 4 (21%) | 0.80 | 0.28-2.21 | 0.66 |
Moderate/severe persistent | 59 | 14 (24%) | 0.90 | 0.44-1.81 | 0.77 |
Sensitization to indoor allergens | 25 | 8 (32%) | 1.41 | 0.73-2.71 | 0.31 |
Sensitization to outdoor allergens | 16 | 6 (38%) | 1.66 | 0.82-3.35 | 0.19 |
Sensitization to both indoor and outdoor allergens | 112 | 23 (21%) | 0.60 | 0.34-1.05 | 0.08 |
OR = odds ratio, CI = confidence interval, FEV1= force expiratory volume in 1 s, FEF25–75 = force expiratory flow during 25-75 second, *
International Study of Asthma and Allergies in Childhood (ISAAC) standardized questionnaire showed that the prevalence of asthmatic symptoms ranged from 2.1% to 32.2% [2]. In Thailand, the ISAAC phase three survey showed that 13.9%–25% of children with rhinitis had asthma [1]. Recently, we reported 16.1 % of our patients with AR treated at the ear, nose, and throat (ENT) allergy clinic had concomitant symptoms of asthma [12]. In that study, 15 percent of patients with AR (23 of 153 patients) had abnormal FEV, even though they did not have any lower airway symptoms. Our 15% prevalence of FEV1 abnormality differs from the finding reported by Ciprandi et al. (8% prevalence) even though the standard criteria, the value of FEV, <80% of predicted value was used as the outcome parameter [11]. These 23 cases of our series have been followed up regularly in our ENT allergy clinic to monitor the possibility of lower airway involvement.
Because the definition of asthma is a reversible airway condition, some studies considered ≥ 12 percent change of FEV, after bronchodilator administration as another variable by which to diagnose asthma [23]. In our study, only 4 patients showed >12 percent changes of FEV,.
Ciprandi et al. proposed the FEF25–75 as an early indicator of lower airway involvement [20, 24, 25]. The various cut-off value of FEF25_75 has been proposed, but the consensus of cut-off value has not yet been established. When using the criteria of FEF25–75 less than 80% of predicted value as suggested [26], the prevalence of abnormal FEF25–75 was 24.2% (37/153 patients) in our study. The prevalence of our abnormal FEV25–75 was higher than the finding of Ciprandi et al. (11%) in 2009.
Several clinical parameters may influence the abnormality of spirometry. For example, duration of rhinitis had been shown to be moderately correlated (Pearson’s correlation coefficient = 0.36) with the abnormality of FEV1 [26]. Our data showed the longer duration of AR (especially a duration >10 y) affected the FEF25–75. This data is consistent that reported by Ciprandi et al. in 2010, who found that patients with a long duration of AR were more likely to develop small airway obstruction [26].
The nasal symptom severity (as measured by total nasal symptom score) has been shown to affect nasal airflow and FEV1 [27]. When nasal symptom severity was classified according to ARIA classification, the majority of our patients were categorized as the moderate-severe/persistent group [16, 28]. The symptom severity, according to ARIA classification, did not show influence on spirometric values either FEV1, percent change of FEV1 or FEF25–75 in our study.
Spirometry can show sensitization to outdoor and indoor allergens. Ciprandi etal. [26] showed significant influence of pollen allergen
An explanation for the differences in prevalence of spirometric abnormalities and risk factors between our present study and the various studies conducted in Europe are proposed as follows. First, allergens in Thailand differ from those in Europe or North America, for instance birch, hazel, and olive trees are rare in Thailand. Second, the severity of AR has been classified according to ARIA instead of a visual analog scale. Last, in tropical countries, a pattern of perennial AR is more prevalent than seasonal AR.
Although the present study provides information regarding the prevalence of abnormal spirometry
results in patients with AR, it has some limitations. First, patients may not be presenting lower airway obstruction on the occasion of the examination, but on different occasions bronchospasm may develop. The application of allergen-specific nasal provocation tests in combination with spirometry in patients with AR showed that allergic nasal reactions may lead to the development of upper and/or lower ventilation obstruction in patients with AR and previously normal spirometry [31, 32]. Second, other spirometry variables such as forced vital capacity (FVC) or the ratio of FEV1 to FVC were not included in the interpretation. Third, the possibility that other unrecognized lower airway conditions (such as occult bronchiectasis) might interfere with interpretation of spirometrie abnormality cannot be excluded. Nevertheless, this study included the patients with AR without any lower airway symptoms, without abnormal chest x-ray, and who were nonsmokers. Moreover, all participants stopped antiallergic medication for one week before the day of spirometry, because of the allergen skin prick test was performed on the same day. These modalities would reduce the possibility of confounding factors affecting pulmonary function test interpretation.
In patients with AR who had no symptoms of lower airway, the prevalence of abnormal FEV1 (<80% of predicted value) and abnormal percent change of FEV1 (≥12%) after bronchodilator were 15% and 2.6% respectively. The early predictor of small airway obstruction (FEF25–75) was abnormal in 24.2%. The sensitization to both indoor and outdoor allergens significantly affected FEV1 abnormality. A duration of allergy more than 10 y significantly affected FEF25–75. When patients with AR seek treatment, the lower airway status should always be evaluated. Awareness of upper and lower airway linkage will lead to early and proper treatment before significant deterioration of lower airway function occurs. A suspicion of bronchial asthma should be raised especially in patients from an AR subgroup.