Methacholine bronchial challenge effects on nasal symptoms and function in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis and asthma may be associated, bronchial hyperreactivity (BHR) is quite common in AR patients. It has been reported that allergen bronchial challenge induces nasal inflammation. Methacholine (MCH) is a stimulus able to elicit BHR. There is no study that investigated the effect of MCH bronchial challenge on the nose. OBJECTIVE: The aim of this study was to evaluate whether MCH bronchial challenge is able to induce changes in nasal symptom perception and nasal function in patients with AR. METHODS: 122 patients (117 males, median age 28 years) suffering from AR were evaluated. Values for bronchial function (FVC, FEV1, FEF25-75, and FEV1/FVC ratio), MCH bronchial challenge, VAS for nasal and bronchial symptoms, and nasal airflow and resistance were assessed. RESULTS: 23 patients (18.9%) had BHR. MCH bronchial challenge induced a significant reduction of nasal obstruction perception (p<0.001), but did not affect the nasal function. Most of patients (91) did not perceive impairment of respiration. The perception of nasal obstruction was strongly related to the AR duration (r=0.65). The highest values of both baseline rhinoVAS and Δ bronchial VAS predicted BHR (OR 1.7 and 2.9 respectively). CONCLUSIONS: The present study demonstrates that in AR patients MCH bronchial challenge does not substantially affect nasal symptoms and function, also in subjects with an acute bronchospasm, such as in BHR patients. However, severity of nasal obstruction perception might predict BHR.

Impaired spirometry may suggest sensitization.

The present study confirms that sensitization is very frequent in the general population and suggests that impaired FEF25-75 may be a marker of sensitization. Therefore, when spirometry is abnormal, mainly concerning FEF25-75, sensitization should be suspected.

Impaired FEF25-75 may predict high exhaled nitric oxide values in children with allergic rhinitis and/or asthma.

Allergic rhinitis and asthma are closely associated. Inflammation is a common pathological characteristic shared by both disorders. The measure of the fractional concentration of exhaled nitric oxide (FeNO) may be considered a surrogate marker for airway inflammation. Forced expiratory flow between 25 and 75 percent of vital capacity (FEF25-75) has been previously demonstrated to be able to predict BHR and bronchial reversibility. The aim of this study was to evaluate whether impaired FEF25-75 values may be related to FeNO values in a pediatric cohort of allergic subjects. 850 children with allergic rhinitis, allergic asthma, or both, were evaluated. Bronchial function (FEV1, FVC, and FEF25-75), FeNO, and sensitizations were assessed. Bronchial function and FeNO were significantly different in the 3 groups (p less than 0.001). A strong inverse correlation between FeNO and FEV1was found in patients with rhinitis, asthma and asthma with rhinitis (r= -0.72, r=-0.70 and r= -0.70, respectively). Impaired FEF25-75 values (such as less than 65 percent of predicted) were significantly associated with high FeNO levels (such as =34 ppb). In conclusion, this study provided evidence that FEF25-75 is strongly and inversely related with FeNO and FEF25-75 may predict high FeNO levels in children with allergic rhinitis, asthma or both.

Impaired FEF25-75 values may predict bronchial reversibility in allergic children with rhinitis or asthma.

FEV1 is considered an important parameter for asthma diagnosis and follow-up. However, it has been proposed that FEF25-75 could be more sensitive than FEV1 to detect slight airways obstruction. Bronchial reversibility defined by positive response to bronchodilation test. The aim of the present study was to define whether an impaired FEF25-75 value (less than 65 percent of predicted) may be predictive for reversibility in a large cohort of allergic children with rhinitis or asthma. Six hundred allergic children were recruited: 300 with controlled asthma and 300 with allergic rhinitis. All of them were evaluated by performing spirometry, bronchodilation test, and skin prick test. Two predictors were significantly associated with bronchial reversibility: i) an impaired FEF25-75 value (less than 65 percent of predicted), and ii) sensitization to perennial allergens. It was more relevant in children with rhinitis (ORAdj:8.9 and 2.2 respectively). In conclusion, this study, conducted in real life, could suggest that an impaired FEF25-75 value (less than 65 percent of predicted) may be considered a reliable marker of bronchial reversibility, mainly in children with allergic rhinitis.

Bronchodilation test in patients with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) may be considered a risk factor for the onset of asthma. Recently, it has been reported that forced expiratory flow between 25% and 75% of vital capacity (FEF25₋75) may predict a positive response to bronchodilation test in asthmatic children. The aim of this study was to evaluate a large group of adult AR patients to investigate the frequency of response to bronchodilation test and FEF25₋75 values. METHODS: One thousand four hundred and sixty-nine consecutive patients suffering from persistent AR were evaluated. Clinical examination, spirometry, and bronchodilation test were performed in all patients. RESULTS: In this study, 62.9% of patients had reversibility to bronchodilation test and 17.8% had impaired FEF25₋75 values (≤ 65% of predicted). Impaired FEF25₋75 values associated with longer rhinitis duration may predict reversibility to bronchodilation test (OR = 11.3; P < 0.001). In addition, a FEF25₋75 cutoff value ≤ 71% of predicted may already discriminate patients with reversibility. CONCLUSIONS: This study highlights that about two-thirds of patients with persistent AR may be considered at risk of becoming asthmatic. This finding should be adequately considered as a precocious spirometry may allow the early detection of patients prone to develop asthma and consequently to treat them.

Visual analogue scale assessment of nasal obstruction might define patients candidates to spirometry.

BACKGROUND: Asthma may be frequently associated with allergic rhinitis. Bronchial obstruction is a characteristic of asthma and spirometry is a cardinal step in asthma diagnosis. However, spirometry is rarely suitable in medical office. Visual Analogue Scales (VAS) is frequently used in common practice. OBJECTIVE: This study aimed at evaluating the suitability of the use of VAS assessment of nasal obstruction to define patients with allergic rhinitis candidates for spirometry. METHODS: 1728 patients with allergic rhinitis were consecutively evaluated. Clinical examination, skin prick test, VAS assessment, and spirometry were performed in all patients. RESULTS: 7.9% of patients had impaired FEV1 values and 24.5% had impaired FEF25-75 values. A VAS value < 3.3 might identify with good reliability patients with impaired FEF25-75 values, such as having initial bronchial airflow limitation. CONCLUSIONS: This study, performed in a large cohort of subjects, highlights the close link between upper and lower airways and shows the possible suitability of the use of nasal obstruction VAS assessment to define patients with allergic rhinitis candidates for spirometry.

Rupatadine improves nasal symptoms, airflow and inflammation in patients with persistent allergic rhinitis: a pilot study.

Nasal obstruction is the main symptom in patients with allergic rhinitis and may be measured by rhinomanometry. Rupatadine is a new antihistamine with potential antiallergic activities. The aim of this pilot study is to evaluate nasal symptoms, nasal airflow and nasal mediators in patients with persistent allergic rhinitis, before and after treatment with rupatadine. Twenty patients with persistent allergic rhinitis were evaluated, 15 males and 5 females (mean age 35 +/- 9.1 years), all of whom received rupatadine (10 mg/daily) for 3 weeks. Nasal and ocular symptoms (measured by VAS), rhinomanometry, and nasal mediators (ECP and tryptase) were assessed in all subjects before and after treatment. Rupatadine treatment induced significant symptom relief (both nasal and ocular, respectively p=0.005 and p=0.0004), including obstruction (p=0.0015) and significant increase of nasal airflow (p=0.0025). Moreover, there was a significant difference of nasal mediators. In conclusion, this pilot study demonstrates the effectiveness of rupatadine treatment in: i) improving nasal and ocular symptoms, ii) increasing nasal airflow, iii) exerting antiallergic activity in patients with persistent allergic rhinitis. These positive results could explain the effectiveness of rupatadine in the treatment of persistent allergic rhinitis, as reported in a previous study Further controlled studies need to be conducted to confirm these preliminary findings.

Visual analogue scale assessment of respiration might be a surrogate for spirometry in allergic rhinitis.

Allergic rhinitis (AR) may be frequently associated with or precede asthma. Bronchial involvement in AR is usually detected by spirometry, however, spirometers are rarely available. The aim of this study is to verify the suitability of the use of visual analogue scales (VAS) as a surrogate for screening spirometry in assessing respiration in AR patients. One hundred twenty patients with allergic rhinitis were studied. VAS for respiration assessment and spirometry were performed in all patients. There was a significant, though weak, relationship between VAS assessment of respiration and FEV(1) (p=0.0076; r=0.244). In conclusion, this preliminary study suggests the use of VAS as screening to assess the respiration of patients with allergic rhinitis who may be candidates for spirometry.

Assessment of the bronchodilation test by visual analog scale in the selection of patients with rhinitis for screening spirometry.

BACKGROUND: The nose and bronchi are closely linked, and rhinitis often precedes the onset of asthma. Bronchial obstruction is a characteristic of asthma, and demonstration of its reversibility is a key element in diagnosis. However, reversibility testing requires a spirometer, which is rarely available in the doctor's office. Visual analog scales (VAS) are frequently used in daily practice. OBJECTIVE: This study evaluated the suitability of a VAS for assessing bronchodilation in patients with persistent allergic rhinitis as a means of selecting candidates for screening spirometry. METHODS: We evaluated 120 patients with moderate to severe persistent allergic rhinitis. All patients underwent a clinical examination, skin prick test, spirometry, bronchodilation test, and VAS. RESULTS: Patients with rhinitis showed significantly increased forced expiratory volume in the first second (FEV1) after the bronchodilation test (median, 11.5%). Positive results were observed in 60%, and VAS values increased (>30%) after the test. There was a significant relationship between deltaVAS and deltaFEV1 (P<.0001; r=0.482). CONCLUSION: This preliminary study shows that patients with moderate to severe persistent allergic rhinitis often experience an increase in FEV1 after the bronchodilation test. VAS assessment of the test might be useful when selecting candidates for spirometry for possible bronchial involvement.

Impact of allergic rhinitis on asthma: effects on bronchial hyperreactivity.

BACKGROUND: Remarkable relationship exists between upper and lower airways. Bronchial hyperreactivity (BHR) is a paramount feature of asthma and may be considered a strong risk factor for the onset of asthma in patients with allergic rhinitis. OBJECTIVE: This study is aimed at evaluating the presence of BHR in a large group of patients with moderate-severe persistent allergic rhinitis alone, and at investigating possible risk factors related to severe BHR. METHODS: Three hundred and forty-two patients with moderate-severe persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test, spirometry and bronchial methacholine (MCH) test were performed in all patients. RESULTS: Twenty-two (6.4%) patients had severe BHR, 74 (21.6%) patients had mild BHR and 192 (56.2%) had borderline BHR; 54 (15.8%) patients had a negative MCH test. The logistic regression analysis evidenced that trees and house dust mites sensitization (ORAdj: 8.1), rhinitis duration > 5 years (ORAdj: 5.4) and FEV1 < or = 86% of predicted (ORAdj: 4.0) were significantly associated with severe BHR. The discriminative ability of this model is appreciably satisfactory, being the AUC = 0.90. CONCLUSION: This study highlights the close link between upper and lower airways and the role of some risk factors, such as tree and mite sensitization, > 5-year duration, and < or = 86% FEV1 values, as risk factors for severe BHR in patients with moderate-severe persistent allergic rhinitis alone. Therefore, BHR is frequently present in patients with chronic rhinitis and should be suspected in the presence of defined risk factors.

Ebastine increases IFN-gamma production in patients with persistent allergic rhinitis.

Nasal obstruction is a leading symptom in patients with allergic rhinitis and depends on inflammation characterized by Th2 polarization. Thus, IFN-gamma is typically deficient in allergic patients. It has been previously reported that ebastine is able to reduce Th2-dependent cytokines. The aim of this study is to preliminarily evaluate IFN-gamma production by peripheral blood mononuclear cells (PBMNC) and clinical changes after a treatment with lyophilized ebastine in patients with persistent allergic rhinitis (PER). Ten patients with PER were evaluated, 7 males and 3 females (mean age 32.4 +/- 6.2 years), all of whom received lyophilized ebastine (20 mg/daily) for 3 weeks. Total nasal symptom score (TSS), subjective evaluation score by visual analogue scale (VAS), and rhinomanometry were evaluated in all subjects before and after treatment. IFN-gamma production by peripheral blood mononuclear cells (PBMNC) was evaluated using different stimuli, in un-treated and ebastine-treated allergic patients by ELISPOT. Ebastine treatment induced significant increase of IFN-gamma production stimulated by grasses (p<0.0001) and Dermatophagoides farinae (p=0.0015). This effect was significantly related with TSS and VAS improvement after treatment (p=0.0038 and 0.004 respectively). In conclusion, this preliminary study demonstrates the effectiveness of ebastine treatment in increasing IFN-gamma production. The clinical relevance of this study is that the clinical improvement is related to the immunologic activity.

Impact of allergic rhinitis on asthma: effects on spirometric parameters.

BACKGROUND: Close association exists between allergic rhinitis and asthma. Moreover, allergic rhinitis is a strong risk factor for the onset of asthma in adults. This study was aimed at evaluating a large group of patients with moderate-to-severe and persistent allergic rhinitis alone for investigating the presence of spirometric abnormalities and possible risk factors related to it. METHODS: A total of 392 patients with persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test and spirometry were performed in all patients. RESULTS: There were 24 (6.1%) patients with forced vital capacity (FVC < 80%) of predicted, 50 (12.8%) with forced expiratory volume in the first second (FEV(1) < 80%) of predicted and 341 (87.0%) with forced expiratory flow at 25% and 75% of the pulmonary volume (FEF(25-75)) < 80% of predicted. The logistic regression analysis evidenced that rhinitis duration (OR(Adj): 1.9/year) and sensitization to house dust mites (OR(Adj): 8.2) were significantly associated with impaired values of 2 or 3 spirometric parameters. CONCLUSION: This study highlights the close link between upper and lower airways and the role of some risk factors, such as duration and mites sensitization, as early prognostic markers of bronchial involvement in patients with moderate-to-severe and persistent allergic rhinitis alone.

A pharmacokinetic interaction study of docetaxel and cisplatin plus or minus 5-fluorouracil in the treatment of patients with recurrent or metastatic solid tumors.

BACKGROUND: The purpose of this study was to look at the pharmacokinetics of docetaxel, cisplatin-derived platinum and 5-fluorouracil (5-FU), when used in combination, to exclude potential clinically relevant pharmacokinetic interactions. METHODS: Fifteen patients with recurrent or metastatic solid tumors were randomized to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 in the first treatment course on day 1 and the same combination plus 5-FU 750 mg/m2/day on days 1-5 in the second course, or the two treatment courses in reversed order. Cycles were repeated every 3 weeks. A pharmacokinetic analysis was performed during the first two cycles. RESULTS: Full pharmacokinetic data was available for 12 of the 15 patients. Treatment was tolerated well, with frequency of toxicity consistent with the safety profile known for docetaxel, cisplatin and 5-FU. Mean clearance values for docetaxel and cisplatin showed no statistically significant difference across the "triple" and the "double" combination treatments, and the mean pharmacokinetic parameters of all agents were within the ranges for previously reported single agent treatment. CONCLUSION: No clinically relevant pharmacokinetic interactions between docetaxel, cisplatin and 5-FU used in combination were noticed in this study.

Screening spirometry to detect respiratory allergy.

BACKGROUND: Recently, it has been evidenced that the forced expiratory flow at the 25 and 75% of the pulmonary volume (FEF25-75) might be considered as a possible marker of early bronchial impairment in patients with allergic rhinitis alone. OBJECTIVES: The aim of this study was to determine whether a spirometric impairment may predict allergy during screening visit. METHODS: The study included 283 Navy soldiers (255 males, mean age 27.1 + 8.2) who had to undergo spirometry for attending specific courses. Fifty-four showed slight spirometric anomalies. Thus, they referred to Navy Hospital of La Spezia for standardized tests: skin prick test, spirometry, and methacholine bronchial challenge. RESULTS: Forty seven (87%) subjects were sensitized (47% monosensitized and 53% polysensitized). Allergic rhinitis was diagnosed in 25 subjects with median nasal TSS 5. FVC and FEV1 values were normal, whereas FEF25-75 values were reduced (61.8 + 14.8 % of predicted), bronchodilation test was significant for FEF25-75 (82.9 + 16.8% of predicted; p<0.001) only. Bronchial hyperreactivity (BHR) was detected in 28 subjects, all but 1 were sensitized. CONCLUSIONS: This study provides evidence, relevant to clinical care, that mild spirometric impairment may generate the suspect of allergic disorders, thus spirometry could be more frequently performed in general population screening.

Levocetirizine improves nasal symptoms and airflow in patients with persistent allergic rhinitis: a pilot study.

BACKGROUND: Nasal obstruction is the main symptom in patients with persistent allergic rhinitis. Some antihistamines have been demonstrated to be capable of improving this symptom. The aim of this pilot study was to evaluate nasal symptoms, nasal airflow, and decongestent activity in patients with persistent allergic rhinitis, before and after treatment with levocetirizine or placebo. METHODS: Forty patients with persistent allergic rhinitis were evaluated, 35 males and 5 females (mean age 23.3 +/- 5.9 years). All of them received levocetirizine (5 mg/daily) or placebo for 4 weeks. The study was double-blind, parallel-group, placebo-controlled, and randomized. Total symptom score (including: nasal itching, sneezing, rhinorrhea, and nasal obstruction) was assessed before and after treatment. Rhinomanometry and decongestion test were performed in all subjects before and after treatment. RESULTS: Levocetirizine treatment induced: significant symptom relief (p<0.001), improved nasal airflow (p<0.001), reduction of reversibility percentage (p<0.05), and increase of total airflow after decongestion test (p<0.03). Placebo did not improve nasal symptoms and airflow. CONCLUSIONS: This pilot study demonstrates the effectiveness of levocetirizine in: i) relieving nasal symptoms, including obstruction, ii) improving nasal airflow, and iii) exerting decongestant activity. Thus, these findings are the first evidence of the impact on airflow and the decongestant activity exerted by levocetirizine in persistent allergic rhinitis.

Sublingual specific immunotherapy reduces PBMC proliferations.

BACKGROUND: Subcutaneous specific immunotherapy has been demonstrated capable of inducing T regulatory response. There is few evidence concerning immunological changes induced by sublingual immunotherapy. OBJECTIVE: The aim of this study was to evaluate T cell proliferation in subjects successfully treated with SLIT for HDM. METHODS: PBMCs were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic and healthy control subjects. After 3 and 6 days of in vitro stimulation with PHA, Candida albicans, Dermatophagoides farinae, grasses, Parietaria judaica, and cat, proliferation. RESULTS: Subjects treated with SLIT showed significant reduction of proliferation induced by Candida albicans, Parietaria, and grasses in comparison with untreated atopics (p=0.0002, 0.0033, and 0.009 respectively). CONCLUSION: This pilot study confirms reduced T cell proliferation in allergic subjects treated with SLIT.

Bronchial hyperreactivity and spirometric impairment in patients with allergic rhinitis.

BACKGROUND: The Link between allergic rhinitis and asthma is well known. Bronchial hyperreactivity (BHR) may be present in rhinitics. The present study is aimed at evaluating a large group of subjects suffering from allergic rhinitis alone to investigate the presence of spirometric impairment and BHR both during and outside the pollen season. METHODS: 360 rhinitics (subdivided in 3 groups: seasonal, SAR, perennial, PAR, and polysensitized, PolysR) were investigated by spirometry and methacholine challenge. RESULTS: There was a significant seasonal difference concerning the number of rhinitics with impaired FEV1 (p<0.01 for SAR, p<0.02 for PAR, and p<0.03 for PolysR) and FEF25-75 (p<0.05 for SAR, p<0.03 for PAR, and p<0.05 for PolysR) as well as with BHR (p<0.05 for SAR and p<0.03 for PAR). CONCLUSIONS: This study evidences that an impairment of spirometric parameters and BHR may be observed in patients with allergic rhinitis alone. Thus, careful evaluation of lower airways should be performed in patients with allergic rhinitis alone.