Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis

BACKGROUND: Bronchial hyperresponsiveness (BHR) and airway inflammation are frequently associated with allergic rhinitis, and may be important risk factors for the development of asthma. Specific immunotherapy (SIT) reduces symptom in subjects with allergic rhinitis, but the mechanisms are not clear. AIMS OF THE STUDY: To assess the effect of Parietaria-SIT on asthma progression, rhinitic symptoms, BHR, and eosinophilic inflammation. METHODS: Nonasthmatic subjects with seasonal rhinitis were randomly assigned to receive Parietaria pollen vaccine (n = 15) or matched placebo (n = 15). Data on symptoms and medication score, BHR to methacholine, eosinophilia in sputum were collected throughout the 3-year study. RESULTS: By the end of the study, in the placebo group, symptoms and medication scores significantly increased by a median (interquartile range) of 121% (15-280) and 263% (0-4400) respectively (P < 0.01), whereas no significant difference was observed in the SIT group. We found no significant changes in sputum eosinophils and BHR to methacholine in both groups throughout the study. Nine of 29 participants developed asthma symptoms during the study; of these, only two subjects (14%) in the SIT-treated group (P = 0.056). CONCLUSIONS: Parietaria-SIT reduces symptom and rescue medication scores, but no changes in BHR to methacholine or sputum eosinophilia were observed. Moreover, Parietaria-SIT appears to prevent the natural progression of allergic rhinitis to asthma, suggesting that SIT should be considered earlier in the management of subjects with allergic rhinitis.     

Determinants of increased exhaled nitric oxide in patients with suspected asthma

Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FE(NO) levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P=0.04), but for high levels of FE(NO) (> or =3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P <0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P >0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.     

Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing

BACKGROUND: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. METHODS: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. RESULTS: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r= -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r= -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. CONCLUSIONS: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.     

The use of exhaled nitric oxide concentration to identify eosinophilic airway inflammation: an observational study in adults with asthma

BACKGROUND: Assessment of eosinophilic airway inflammation may be helpful in the management of asthma. Nitric oxide (NO) has potential advantages as a tool to monitor airway inflammation although little is known about the relationship between NO and eosinophilic airway inflammation and the factors which influence it. METHODS: We set out to define the relationship between exhaled NO and the sputum eosinophil count, identify the exhaled NO concentration that best identified a sputum eosinophil count >3% and investigate the impact of several potential confounding factors in 566 consecutive patients with varying severity of asthma. Finally we examined the ability of exhaled NO concentrations measured at differing exhalation flows to identify the presence of a sputum eosinophilia. RESULTS: We found a significant positive relationship between exhaled NO and sputum eosinophil count (R(2)=0.26, P<0.001) which was best described using a non-linear model. There were no clinically important confounding factors to this model. In non-smokers an exhaled NO concentration of >8.3 p.p.b. at 250 mL/s gave 71% sensitivity and 72% specificity for identifying a sputum eosinophil count of >3%. CONCLUSIONS: This value of exhaled NO would seem to be the best for identifying significant eosinophilic airway inflammation. It is applicable to a wide range of non-smoking patients with asthma; exhalation flow does not alter the ability of exhaled NO concentration to detect a sputum eosinophilia.     

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.     

Eosinophilic airway inflammation and the prognosis of childhood asthma

BACKGROUND: Eosinophilic airway inflammation is a key pathophysiological feature of asthma that can predict treatment response. However, the prognostic value of sputum eosinophilia is not established. OBJECTIVE: The aim of this study was to determine the influence of induced sputum eosinophilia on the prognosis of childhood asthma. METHODS: A cohort of children with asthma was evaluated by induced sputum analysis at inception and classified as having either eosinophilic asthma (EA) (sputum eosinophils >2.5%) or non-eosinophilic asthma (NEA). After a mean follow-up period of 5 years, eligible subjects (n=83) were contacted and 69 subjects (33 EA, 36 NEA) evaluated. The children had a mean age of 15.9 years, and 61% were male. RESULTS: Children with EA reported more wheeze during the follow-up period (27% vs. 6% wheezed most years; P<0.0001), increased night waking during the past 12 months (28% vs. 3% reported weekly waking; P=0.01), and greater impairment of quality of life due to asthma (P=0.04). Subsequent beta2-agonist use was increased in children with EA (P=0.02), although there was no difference in corticosteroid use. In EA, subsequent forced expiratory volume in 1 s/forced vital capacity was lower (79% vs. 86%; P=0.01) and grass pollen allergy was more prevalent (77% vs. 27%; P=0.006). CONCLUSION: In children, eosinophilic airway inflammation is associated with deteriorating asthma over time. This is consistent with the hypothesis that airway inflammation has an adverse impact on the prognosis of childhood asthma, and suggests a role for monitoring inflammation in asthma management.     

Eosinophilic Airway Inflammation and Airway Hyperresponsiveness According to Aeroallergen Sensitization Pattern in Patients With Lower Airway Symptoms

Purpose

Sensitization to specific allergens may be important in the development of allergic airway inflammation and airway hyperresponsiveness (AHR). We evaluated the effect of specific aeroallergen sensitization on eosinophilic airway inflammation and AHR.

Methods

We reviewed retrospectively the clinical data of subjects who underwent skin prick tests to aeroallergens, induced sputum analysis, and methacholine bronchial provocation tests to evaluate lower airway symptoms as well as analyzed the associations between the pattern of aeroallergen sensitization and sputum eosinophilia or AHR.

Results

Of the 1,202 subjects be enrolled, 534 (44.4%) were sensitized to at least one aeroallergen in skin tests. AHR was demonstrated in 23.5% and sputum eosinophilia in 38.8%. Sputum eosinophilia was significantly associated with sensitization to perennial allergens (OR, 1.9; 95% CI, 1.4-2.5), house dust mite (OR, 1.7; 95% CI, 1.3-2.3), dog (OR, 1.9; 95% CI, 1.1-3.3), and cat (OR, 2.1; 95% CI, 1.4-3.4). AHR was associated with sensitization to perennial allergens (OR, 2.7; 95% CI, 2.0-3.7), house dust mite (OR, 2.2; 95% CI, 1.6 3.2), Alternaria (OR, 2.3; 95% CI, 1.2-4.7), and cat (OR, 2.7; 95% CI, 1.7-4.3). Sensitization to more perennial allergens increased the risk for sputum eosinophilia and AHR. There was no relationship with individual seasonal allergens.

Conclusion

The development of airway eosinophilic inflammation and AHR in an adult Korean population was associated with sensitization to perennial allergens rather than seasonal allergens.     

Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis patients with or without bronchial hyperresponsiveness

BACKGROUND: We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. OBJECTIVE: The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. METHODS: Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. RESULTS: Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%-upper 95% confidence interval (CI) of geometric mean: 1.9-5.1) vs. 1.4 (0.9-2.2) and 0.7 (0.3-1.6) pg/microg total protein] and hyaluronan [0.30 (0.22-0.43) vs. 0.15 (0.10-0.20) and 0.20 (0.12-0.35) ng/microg total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014-0.033) and 0.015 (0.011-0.021) compared with 0.010 (0.007-0.014) ng/microg total protein]. The level of ECP remained elevated off season. CONCLUSION: Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation.     

Bronchial responsiveness to adenosine-5''-monophosphate and methacholine as predictors for nasal symptoms due to newly introduced allergens. A follow-up study among laboratory animal workers and bakery apprentices

BACKGROUND: In asthma patients, bronchial hyper-responsiveness (BHR) to adenosine-5'-monophosphate (AMP) reflects bronchial inflammation more closely than BHR to methacholine. In this follow-up study we studied bronchial responsiveness to both stimuli as predictors of new-onset airway symptoms. METHODS: We included 118 laboratory animal workers and bakery apprentices with a work experience of maximally 1 year. The baseline survey comprised a questionnaire, skin prick tests (SPTs) to common and work allergens, blood eosinophil counting, and bronchial challenge with methacholine and AMP. At follow-up, questionnaire and SPTs to work allergens were repeated. Airway symptoms to common allergens and work allergens were defined as nasal symptoms, chest tightness or asthma attack during or after contact with either common or work allergen. Bronchial challenge tests were analysed by BHR at a 15% fall in forced expiratory volume of 1 s (FEV1), and by dose-response-slope (DRS). RESULTS: Fourteen subjects (12%) developed airway symptoms to work allergens, of whom 12 had nasal symptoms. A positive SPT to work allergens occurred in 64%, and was the strongest predictor of airway symptoms [relative risk (RR) 7.5, 95% confidence interval (CI) 2.0-28.6]. Other predictors were airway symptoms to common allergens (RR 4.3, 95% CI 1.4-12.8), blood hypereosinophilia (RR 4.4, 95% CI 1.2-15.4) and BHR, with a slightly higher risk estimate for AMP than for methacholine (RRAMP 3.7, 95% CI 1.1-12.5 and RRmeth 2.8, 95% CI 1.0-8.5). The difference was more distinct analysing airway responsiveness by DRS, for which AMP predicted symptoms better than methacholine (P < 0.05). CONCLUSIONS: Pre-existent bronchial inflammation or a preinflammatory state marked by AMP (hyper)responsiveness increases the vulnerability to develop nasal symptoms.     

Effect of current exposure to Der p 1 on asthma symptoms, airway inflammation, and bronchial hyperresponsiveness in mite-allergic asthmatics

The existence of a dose-response relationship between indoor allergen exposure and sensitization has been widely described, but the effect of allergen exposure on asthma activity (symptoms, bronchial hyperresponsiveness [BHR], and inflammation) is not clear. Our aim was to determine the existence of an association among current exposure to mite allergens and symptoms, BHR, and airway inflammation assessed in blood and sputum from asthmatic patients sensitized to Dermatophagoides pteronyssinus. We selected 31 mild and recently diagnosed (12-24 months) asthma patients sensitized to D. pteronyssinus. Allergenic exposure (Der p 1, Der 2) was assessed by a commercial assay based on monoclonal antibodies (mAb), carried out on the dust samples collected from patients' beds in a standardized way. Patients completed an asthma symptom questionnaire and underwent skin tests, methacholine bronchial challenge, and sputum induction. Sputum cell profile was analyzed and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin(IL)-5 levels were quantified in sputum supernatant. Total eosinophil numbers and ECP levels were measured in blood samples. Most patients were exposed to Der p 1 levels under 2 microg/g of dust. Der p 1 exposure was higher among the subjects with positive sputum tryptase detection (P = 0.020). Der p 1 levels showed a trend toward correlation with asthma symptoms (P = 0.066, r = 0.36) and correlated with sputum tryptase levels (P = 0.032, r = 0.42). No relationship between BHR, eosinophilic inflammation, and allergenic exposure was found. Our results suggest that asthma symptoms and lung mast-cell activation are at least partially dependent on current allergen exposure. The lack of correlation between mite exposure, eosinophilic inflammation, and BHR supports the role of other factors that enhance the immunologic response initiated by allergen, increasing the activity of asthma.     

House dust mite-specific IgE antibodies in induced sputum are associated with sputum eosinophilia in mite-sensitive asthmatics.

BACKGROUND: Although allergen-specific IgE antibodies have been considered to play an important role in the pathogenesis of atopic asthma, the role of IgE antibodies in the development of airway inflammation is not well defined. OBJECTIVE: To evaluate the association between allergen-specific IgE antibodies and inflammation of the asthmatic airway. METHODS: We measured house dust mite (HDM; Dermatophagoides farinae)-specific IgE antibodies in both serum and induced sputum from 16 HDM-sensitive asthmatic patients, and evaluated their association with sputum eosinophilia and eosinophil cationic protein (ECP) levels in induced sputum. RESULTS: Levels of HDM-specific IgE antibodies in induced sputum were significantly higher in asthmatic patients than in controls (P < .01). In asthmatic patients, levels of HDM-specific IgE antibodies were significantly higher in induced sputum samples with eosinophilia (sputum eosinophil count > or = 5% of 200 counted non-squamous cells) than in those without eosinophilia (P < .05). There were no significant differences in serum levels of HDM-specific IgE antibodies between asthmatic patients with sputum eosinophilia and asthmatic patients without sputum eosinophilia. In asthmatic patients, sputum ECP levels were significantly correlated with levels of HDM-specific IgE antibodies (r = 0.60, P = .01) in induced sputum but not with those in serum. CONCLUSION: We conclude that allergen-specific IgE antibodies in induced sputum from atopic asthmatics are associated with sputum eosinophilia. This result suggests that IgE-dependent mechanisms are involved in eosinophilic inflammation of the airway in atopic asthmatics.     

Cloned Th cells confer eosinophilic inflammation and bronchial hyperresponsiveness

BACKGROUND: The essential role of Th cells and T cell cytokines in eosinophilic inflammation has been established. METHODS: To determine whether Th cells are sufficient for the development of airway eosinophilic inflammation, ovalbumin-reactive murine Th clones were established and infused into unprimed mice. RESULTS: Eosinophilic infiltration into the lung was induced upon antigen inhalation in parallel with the rise in bronchoalveolar lavage fluid (BALF) eosinophil peroxidase activity. Neither IgG, IgA, nor IgE antibodies were present in this model. Pathological examination showed swelling and desquamation of epithelial cells, mucous plugs, and goblet cell hyperplasia, all of which well resemble human asthma. Fluorescent probe labeled Th clones migrated into the lung prior to the eosinophil accumulation. Bronchial hyperresponsiveness (BHR) was clearly induced upon antigen inhalation. Anti-IL-5 monoclonal antibody abrogated the responses. Dexamethasone and cyclosporin A suppressed cytokine production by Th cells both in vitro and in vivo, BALF eosinophilia, and BHR. The number of eosinophils recovered in the BALF correlated with the intensity of BHR. CONCLUSION: The results clearly indicated that monoclonal Th cells are sufficient for the development of both airway eosinophilia and BHR. Agents capable of downregulating IL-5 production seem promising for the treatment of bronchial asthma.     

Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in patients with allergic rhinitis

There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59 mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.     

Nasal eosinophilia: an indicator of eosinophilic inflammation in asthma

Background It is noteworthy that there is a clear clinical, epidemiological and pathophysiological association between upper and lower airway inflammation in rhinitis and asthma. Objective The aim of this study was to compare the eosinophil counts in induced sputum and nasal lavage fluids in asthma, checking their association and the accuracy of nasal eosinophilia as a predictor of sputum eosinophilia by a cross‐sectional study. Methods The clinical evaluation, asthma control questionnaire (ACQ), pre‐ and post‐bronchodilator spirometry, nasal and sputum sample was performed. The nasal eosinophilia was analysed by a receiver operating curve and logistic regression model. Results In 140 adults, the post‐bronchodilator forced expiratory volume in 1 s (FEV₁) did not differ between patients with or without sputum eosinophilia (0.18). After adjusted for upper airway symptoms, age, ACQ score and post‐bronchodilator FEV₁, sputum eosinophilia was associated with 52 times increase in odds of nasal eosinophilia, whereas each 1% increase in bronchodilator response was associated with 7% increase in odds of nasal eosinophilia. Conclusion This study brings further evidence that upper airway diseases are an important component of the asthma syndrome. Furthermore, monitoring of nasal eosinophilia by quantitative cytology may be useful as a surrogate of sputum cytology in as a component of composite measurement for determining airway inflammation.     

Role of FEF25%-75% as a predictor of bronchial hyperreactivity in allergic patients.

BACKGROUND: The small airways may play an important role in the clinical manifestations of asthma. Forced expiratory flow between 25% and 75% (FEF25%-75%) has been proposed as an approximate measure of the caliber of distal airways. Bronchial hyperreactivity (BHR) is a feature of asthma. OBJECTIVE: To evaluate the possible role of FEF25%-75% as a predictor of BHR in allergic patients with asthma and rhinitis. METHODS: A total of 726 patients (mean +/- SD age, 24.7 +/- 6.3 years) were evaluated. Spirometry and methacholine bronchial challenge were evaluated in all the participants. RESULTS: A difference between forced expiratory volume in 1 second and FEF25%-75% greater than 20 or a ratio between these variables greater than 1.24 discriminates between patients with no response to a mild response to methacholine vs patients with a moderate-to-severe response with high sensitivity (P < .001). CONCLUSION: This study highlights the possible role of FEF25%-75% in predicting BHR in allergic individuals with airway disorders.     

Negative association of Enterobius infestation with asthma and rhinitis in primary school children in Taipei

BACKGROUND: The relationship between allergy and parasites has been controversial, especially in non-tropical countries. Enterobius vermicularis (human pinworm) is the most prevalent intestinal parasite in industrialized countries. OBJECTIVE: To examine the association between pinworm infestation and allergy in primary school children. METHOD: Peri-anal tape test for pinworm is routinely performed in Taipei primary schools. We collected data from school records and questionnaires distributed to all children in four primary schools grades 1 through 6 (n = 3107). RESULTS: The prevalence of physician-diagnosed asthma (9.3% vs. 14.1%, P = 0.007) and allergic rhinitis (27.4% vs. 38.3%, P = 0.001) was lower in pinworm-positive compared to uninfested children. Pinworm was not correlated with atopic dermatitis or parent allergy. With logistic regression controlling for sex, parent allergy and lower respiratory infection, current asthma (OR = 0.25, 95% CI 0.10-0.63) and rhinitis (OR = 0.61, 95% CI 0.45-0.84) were negatively associated with pinworm. Among children in grades 3-6 who had no asthma or rhinitis before age 7, those with early infestation (pinworm diagnosis at or before grade 1) had a lower risk of having diagnosis of rhinitis during school years, compared to the uninfected group (5.4% vs. 12.3%, P = 0.03; adjusted OR = 0.47, 95% CI 0.21-1.02). CONCLUSIONS: We identified a negative association between pinworm infestation and allergic airway diseases, which could in part be attributed to protective effect of pinworm infestation on development of allergic symptoms. Other mechanisms of association could not be ruled out.     

Dissimilarity between seasonal changes in airway responsiveness to adenosine-5'-monophosphate and methacholine in patients with grass pollen allergic rhinitis: relation to induced sputum

BACKGROUND: In patients with allergic rhinitis, bronchial hyperresponsiveness (BHR) and airway inflammation may increase during pollen exposure. BHR can be assessed by adenosine-5'-monophosphate (AMP) or methacholine challenge. It has been suggested that BHR to AMP is more closely related to airway inflammation than BHR to methacholine. Seasonal allergic rhinitis offers a dynamic model to study changes in BHR and airway inflammation during natural allergen exposure. METHODS: We measured BHR [provocative concentration causing a 20% fall (PC(20)) in forced expiratory volume in 1 s (FEV(1))] to AMP and methacholine, and induced sputum cells in 16 rhinitis patients before and during the 2001 grass pollen season. RESULTS: There was a decrease in PC(20) methacholine during pollen exposure (geometric mean PC(20) from 3.22 to 1.73 mg/ml, p = 0.0023), whereas no reduction was observed for PC(20) AMP (p = 0.11). There was no increase in sputum eosinophils [pre: 0.69% (95% confidence interval 0.22-2.07); during: 1.85 (0.55- 5.6), p = 0.31]. Although the correlation of log PC(20) methacholine and log PC(20) AMP at baseline was good (r = 0.76, p = 0.001), individual seasonal changes (doubling concentrations) in PC(20) methacholine were not correlated with changes in PC(20) AMP (rho = 0.21, p = 0.44). There was no correlation between baseline log PC(20) methacholine or seasonal changes in PC(20) methacholine and sputum eosinophils (p > 0.12, all correlations). In contrast, there was a significant correlation between seasonal changes in PC(20) AMP and changes in sputum eosinophils (rho = -0.59, p = 0.025). CONCLUSIONS: These data show dissimilarity between seasonal changes in PC(20) AMP and methacholine in patients with seasonal allergic rhinitis. Moreover, PC(20) AMP seems to be more closely related to sputum eosinophils than PC(20) methacholine. The clinical significance of this discrepancy is unclear.     

Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum

BACKGROUND: Eosinophilic inflammation is a crucial aspect of allergic diseases such as bronchial asthma. An eosinophil-active chemokine, eotaxin, may play a role in the pathogenesis of the tissue eosinophilia accompanying asthma. METHODS: Induced sputa were obtained from 53 patients with atopic asthma and six healthy subjects, and the concentration of eotaxin in the sputum was measured by ELISA. We investigated whether the sputum content of eotaxin is related to 1) asthma status or corticosteroid therapy, and 2) other sputum indices, including percentage of eosinophils and concentration of eosinophil cationic protein (ECP). RESULTS: The patients with stable or unstable asthma showed significantly higher concentrations of sputum eotaxin than the normal controls. The level of sputum eotaxin demonstrated a positive correlation with the percentage of eosinophils in stable asthmatics not receiving corticosteroid therapy, but not in stable patients treated with corticosteroids, or in unstable patients. Sputum eotaxin demonstrated a positive correlation with ECP in asthmatic patients who were either in a stable state or not receiving steroid therapy. CONCLUSIONS: The elevated level of eotaxin detected in association with increased eosinophils and ECP in the sputum of asthmatics suggests that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation. The relationship of eotaxin to airway eosinophilia may be modified by the stability status of asthma and corticosteroid therapy.     

Comparison of allergen-induced changes in bronchial hyperresponsiveness and airway inflammation between mildly allergic asthma patients and allergic rhinitis patients

Bronchial eosinophilic inflammation and bronchial hyperresponsiveness (BHR) are the main features of allergic asthma (AA), but they have also been demonstrated in allergic rhinitis (AR), suggesting a continuity between both diseases. In spite of not fully reproducing natural allergenic exposure, the allergen bronchial provocation test (A-BPT) has provided important knowledge of the pathophysiology of AA. Our aim was to verify the existence of a behavior of AA and AR airways different from the allergen bronchial challenge-induced airway eosinophilic inflammation and BHR changes. We studied a group of 31 mild and short-evolution AA and 15 AR patients, sensitized to Dermatophagoides pteronyssinus. The A-BPT was performed with a partially biologically standardized D. pteronyssinus extract, and known quantities of Der p 1 were inhaled. Peripheral blood (eosinophils and ECP) and induced sputum (percentage cell counts, ECP, albumin, tryptase, and interleukin [IL]-5) were analyzed, before and 24 h after A-BPT. Methacholine BHR, assessed before and 32 h after the A-BPT, was defined by M-PD20 values and, when possible, by maximal response plateau (MRP). The A-BPT was well tolerated by all the patients. AA presented a lower Der p 1 PD20 and a higher occurrence of late-phase responses (LPR). M-PD20 values decreased in AA, but not in AR, patients. MRP values increased in both groups. Eosinophils numbers and ECP levels increased in blood and sputum from both AA and AR, but only the absolute increment of sputum ECP levels was higher in AA than AR patients (P = 0.025). The A-BPT induced no change in sputum albumin, tryptase, or IL-5 values. We conclude as follows: 1) In spite of presenting a lower degree of bronchial sensitivity to allergen, AR patients responded to allergen inhalation with an eosinophilic inflammation enhancement very similar to that observed among AA. 2) MRP levels increased in both AA and AR patients after allergen challenge; however, M-PD20 values significantly changed only in the AA group, suggesting that the components of the airway response to methacholine were controlled by different mechanisms. 3) It is possible that the differences between AR and AA lie only in the quantitative bronchial response to allergen inhalation.     

Sputum eosinophil counts and eosinophil cationic protein levels in cough-variant asthma and in classic asthma, and their relationships to airway hypersensitivity or maximal airway response to methacholine

Background:  The aims of this study were to compare the degree of airway inflammation in cough-variant asthma (CVA) with that in classic asthma (CA), and to examine the relationship between airway inflammation and airway hypersensitivity or maximal airway response to methacholine in both conditions.
Methods:  Sputum was induced in 41 CVA patients, in 41 methacholine PC₂₀-matched CA patients, and in 20 healthy children. The sputum samples were analyzed for total and differential cell counts, and for eosinophilic cationic protein (ECP). A high-dose methacholine challenge test was performed in CVA and CA patients to determine PC₂₀ and maximal airway response.
Results:  Sputum eosinophil percentages and ECP levels were significantly elevated in CVA and CA vs the control, but no significant differences were found between the two asthma groups. In the two asthma groups, neither sputum parameters correlated significantly with methacholine PC₂₀. However, the absence of a maximal response plateau or its higher level, when present, was associated with increased eosinophil percentages and ECP levels in the CVA group.
Conclusions:  The degree of eosinophilic inflammation may not be causally related to differences in presented asthma manifestations. The identification of a maximal response plateau and the level of this plateau in patients with CVA may provide information pertinent to airway eosinophilic inflammation.