Prevalence of impaired lower airway function in Thai patients with allergic rhinitis

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 (FEF_{25 75}), was also recorded and analyzed because some articles proposed this value as a predictor of early airway obstruction [20-22].

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 Table 1.

The mean ± SD of FEV₁ and FEF_25–75 was 98.89 ±11.93 and 95.64 ± 22.42, respectively. Twenty-three cases (15%) had abnormal FEV₁ (Table 2). Four patients had a percent change of FEV₁ higher than 12%. Thirty-seven patients had abnormal FEF_{25– 75}. (Table 2).

Figure 1

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 (Table 3).

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, P < 0.03). There was no association between FEV₁ abnormality and other variables such as duration of allergy, symptom severity, sensitization to indoor allergens only and sensitization to outdoor allergens only (Table 4).

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 (Table 5).

Thirty-seven patients had the value of FEF_25–75 <80% of predicted value. From the univariate analysis, moderate/severe intermittent symptom severity seemed to affect FEF_25–75. Therefore, in the multivariate analysis of symptom severity was not significant.

The duration of allergic symptoms >10 y significantly affected FEF_25–75. Multivariate analysis found duration significantly affected FEF_25–75 (adjusted OR = 2.07; 95%CI = 1.01-4.25, P < 0.05). There was no influence of abnormal percent change of FEF_25–75 on sensitization to indoor or outdoor allergens (Table 6).

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 FEF_25–75 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 FEF_25–75 less than 80% of predicted value as suggested [26], the prevalence of abnormal FEF_25–75 was 24.2% (37/153 patients) in our study. The prevalence of our abnormal FEV_25–75 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 FEF_25–75. 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 FEF_25–75 in our study.

Spirometry can show sensitization to outdoor and indoor allergens. Ciprandi etal. [26] showed significant influence of pollen allergen (P < 0.01) and barely significant of perennial allergens (P < 0.05) on FEV₁ and FEF_25–75. In the present study, sensitization to indoor and outdoor allergens significantly influenced FEV₁ (P < 0.05). By contrast with the studies from Europe, pollen sensitization or allergy showed no influence on FEV₁ in our patient participants [29, 30].

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 (FEF_25–75) 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 FEF_25–75. 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.