Capsaicin cough sensitivity in allergic asthmatic patients increases during the birch pollen season.

BACKGROUND: A change in neural responsiveness may occur as the result of allergic inflammation in the lower airways as well as in the upper airways. In the lower airways, capsaicin cough sensitivity is known to reflect sensory neural reactivity. OBJECTIVE: The aim of this study was to establish whether allergic inflammation changes airway neural sensory reactivity during prolonged allergen exposure. METHODS: Ten nonsmoking patients with birch pollen-allergic asthma performed a capsaicin inhalation challenge twice, once in the off-pollen season and once during the pollen season. The number of coughs and symptoms induced by capsaicin were recorded and compared with those of healthy control subjects. RESULTS: The response to capsaicin, expressed as number of coughs, increased in a dose-dependent manner during both tests. Before the season, the response was similar to that of healthy control subjects, but during the pollen season, the reactivity was significantly increased. Variations in forced expiratory volume in 1 second were not significant before and after each challenge, and values did not change during the pollen season as compared with the winter season. CONCLUSIONS: Sensory reactivity in allergic asthmatic patients may be increased during prolonged allergen exposure as during the pollen season. This finding suggests that allergic inflammation in the lower and/or upper airways may trigger neurogenic mechanisms of significant clinical importance.     

Oxygen radical production by blood eosinophils is reduced during birch pollen season in allergic patients

Background The eosinophil granulocyte takes part in allergic inflammatory diseases, like asthma and rhinitis. The aim of this study was to investigate the oxidative metabolism of the blood eosinophils and neutrophils from birch pollen allergic patients, during and after exposure to their allergen. Methods Thirteen birch pollen allergic patients, with seasonal symptoms of rhinitis, with or without asthma, were followed. The cells were purified using a percoll gradient and the MACS system. The eosinophil purity in all samples was >95%. The oxidative metabolism of both the PMN and the eosinophils was measured by means of a chemiluminescenee (CL) assay, with luminol or lucigenin as the amplifier, and using PMA (16nM) as the activator. Results In relative terms, the lucigenin CL by the eosinophils was 5-10-foId higher than that of the PMN, P= 0.002. The eosinophils of the birch pollen allergic patients produced less oxygen radicals during the season, compared to the reference group, measured both with luminol CL and lucigenin CL, P=0.01 and P= 0.02 respectively. Out of season, there was no difference. There was also no difference, during either period, between patients and references in PMN CL. Separating the eosinophils into hypodense and normodense fractions, showed a decreased oxidative metabolism by the hydrodense eosinophils. Conclusion We conclude that the eosinophils of birch pollen allergic patients have reduced production of oxygen radicals when the patients are exposed to their allergen, which could depend on higher amounts of hypodense eosinophils in the blood during season.     

Priming effect of a birch pollen season studied with laser Doppler flowmetry in patients with allergic rhinitis

Nasal mucosal provocation tests were done on eight patients with seasonal allergic rhinitis before and after a birch pollen season. The effects on nasal microvascular blood flow were detected by means of laser Doppler flowmetry. The patients reacted to the birch pollen provocation with an increase in blood flow. This increase was greater after the pollen season than before, when the same pollen doses were used, indicating a priming phenomenon of the resistance vessels.     

Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season

BACKGROUND:The oesophagus is normally devoid of eosinophils. There are some disorders accompanying with eosinophil infiltration. Food allergy has been reported as a common reason, especially in children but some other studies have also indicated that aeroallergens might have a role in oesophageal eosinophil accumulation. OBJECTIVE:In this study we investigated whether there is any eosinophil recruitment in the oesophagus of pollen-allergic patients who had respiratory symptoms during the season. METHODS:Thirty-eight symptomatic patients (allergic rhinitis (AR) with or without asthma) who had sensitization to grass pollen were included in the study during the pollen season. Controls were composed of 25 healthy non-atopics and 24 patients diagnosed as having gastro-oesophageal reflux disease. Reflux was excluded in allergic and non-atopic groups, whereas the presence of allergy was eliminated in control groups. Gastrointestinal endoscopy was performed in all participants, and biopsy specimens were taken from both the proximal and the distal oesophagus to evaluate eosinophil accumulation. At the same time, blood eosinophil numbers were counted. Results Oesophageal eosinophil accumulation was found in 10 allergic patients (26%) and in five patients (21%) with gastro-oesophageal reflux disease but none of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were higher in these 10 patients than the rest of the 28 patients without infiltration. In this group, blood eosinophils were also correlated with the number of accumulated eosinophils in the oesophagus (P<0.001). There was more intense eosinophil infiltration at the distal part of the oesophagus in the reflux group when compared with the allergic group (mean 7.6+/-5.6 vs. 3.2+/-3.7). Nevertheless, eosinophils were found to be concentrated (mean 5.5+/-7.3) in the proximal oesophagus of allergic patients, although it was 1.7+/-1.5 in reflux patients (P>0.05). Conclusion Our results showed that eosinophil infiltration might be observed in oesophageal tissue of patients with respiratory tract allergy during the symptomatic period. This finding may possibly reflect the systemic and common mucosal aspects of allergic inflammation.     

Immunotherapy abrogates the generation of eosinophil and neutrophil chemotactic activity during pollen season

In a group of 40 birch pollen-allergic patients with a history of rhinoconjunctivitis and wheezing during the pollen season, 20 were immunotherapy (IT) treated preseasonally with birch-pollen extract (Pharmacia, Uppsala, Sweden). Blood samples for determination of the levels of heat-labile eosinophil chemotactic activity (HL-ECA), heat-labile neutrophil chemotactic activity (HL-NCA), and heat-stable neutrophil chemotactic activity were collected before the season, at the beginning of the study, at the start of the season, at the peak, at the end, and after the birch-pollen season. The symptoms from rhinoconjunctivitis and airways, peak expiratory flow, and use of medication were recorded throughout the season. Significant increases of HL-ECA and HL-NCA were observed in untreated compared with IT-treated patients at the start of the season (p less than 0.0001 for both activities) and at the peak of the birch-pollen season (p less than 0.0005 and p less than 0.01, respectively). At the end of the season, HL-ECA levels were not significantly different between the patient groups, whereas HL-NCA levels were still higher in untreated patients (p less than 0.005). We conclude that IT completely abrogates the generation of HL-ECA and HL-NCA during a pollen season.     

Efficacy and safety of birch pollen immunotherapy for local allergic rhinitis

Background

Local allergic rhinitis (LAR) is a relatively new disease.

Oral immunotherapy in birch pollen hay fever

Previous controlled trials with oral administration of allergen have not demonstrated any treatment effect in patients with allergic rhinoconjunctivitis or asthma. In the present double-blind, placebo-controlled trial, we have tested the effect of oral immunotherapy in adult patients with birch pollinosis. Thirty-nine patients completed this 18-month study comprising two birch pollen seasons. The patients received enterosoluble capsules daily, and the actively treated patients reached a cumulated dose of 280 times 10(6) biologic units of birch pollen extract, which is about 200 times higher than the dose used in conventional subcutaneous immunotherapy. We found a significant decrease in eye symptom scores and conjunctival sensitivity to birch pollen, as determined by conjunctival provocation test, as well as a numerical but nonsignificant decrease in nasal symptom scores, nasal sensitivity as determined by nasal provocation test, and antiallergic medication. The treatment was safe, and only a few slight side effects were observed. We thus conclude that our study demonstrates a clinical effect of oral immunotherapy in birch pollinosis.     

Demonstration of mast cell chemotactic activity in bronchoalveolar lavage fluid collected from asthmatic patients before and during pollen season

BACKGROUND: Mast cells are versatile effector cells of primary importance in asthma and airway inflammation. During inflammation mast cells accumulate in the bronchial epithelium. The mechanism for this increase in mast cell number has not been defined. OBJECTIVES: The aim of this study was to examine the presence of mast cell chemotactic activity in bronchoalveolar lavage (BAL) fluid taken before and at the end of 2 pollen seasons from patients with allergic asthma. METHODS: To measure mast cell chemotactic activity, we used a modified Boyden chamber and the human mast cell line HMC-1 or in vitro-developed mast cells as responder cells. RESULTS: A total of 27 patients were investigated, of which 8 exhibited mast cell chemotactic activity in their BAL fluid collected before season. A significant increase in the activity was found in 18 of 27 BAL fluids sampled at the end of the pollen season. No difference was found between patients treated with immunotherapy or placebo. The presence of stem cell factor could be detected in all BAL fluids analyzed. Blocking antibodies against stem cell factor or transforming growth factor-beta partially blocked the activity in some of the BAL fluids. Treatment of the responder cells with pertussis toxin reduced the migratory activity in 13 of 14 BAL fluids collected during pollen season. CONCLUSION: This study demonstrates the presence of mast cell chemotactic activity in BAL fluids from patients with allergic asthma, with a significant increase in activity during pollen season. The major part of this activity consisted of factors mediating their effect through G(i)-protein coupled receptors. This activity may be responsible for the mast cell accumulation in the intraepithelial layer seen in allergic asthmatic patients.     

Classification and management of allergic rhinitis patients in general practice during pollen season

BACKGROUND: Allergic rhinitis (AR) represents a major challenge in primary care. The Allergic Rhinitis and its Impact on Asthma (ARIA) group proposed a new classification for AR and developed evidence-based guidelines for the management of this disease. We conducted this study to further characterize the classes of AR described by ARIA, and to evaluate whether the management of AR in general practice is in accordance with the ARIA guidelines. METHODS: During the pollen season of 2003, 95 Belgian general practitioners (GPs) enrolled 804 patients who presented with symptoms of AR. For each patient, a questionnaire comprising the clinical presentation and management was completed. RESULTS: In 64% of the patients, AR was classified as intermittent and in 36% as persistent. Persistent rhinitis caused more discomfort than intermittent rhinitis. Only 50% of the patients had ever undergone allergy testing. Among them, 51% were allergic to both seasonal and perennial allergens. Eighty-two per cent of the persistent rhinitics were allergic to at least one seasonal allergen and 72% of the intermittent rhinitics to at least one perennial allergen. When compared strictly with the ARIA recommendations, 49% of the patients with mild and/or intermittent AR were overtreated, whereas about 30% of those with moderate/severe persistent rhinitis were undertreated. CONCLUSION: This study confirms that the previous classification of AR into 'seasonal' and 'perennial' is not satisfactory and that intermittent and persistent AR are not equivalent to seasonal and perennial AR respectively. Furthermore, persistent rhinitis has been shown to be a distinct disease entity. Further efforts are required to disseminate and implement evidence-based diagnostic and treatment guidelines for AR in primary care practice.     

Assessment of cross-reactivity in patients allergic to birch pollen by immunoblotting

Cross-reactivity related to birch pollynosis and ingestion of certain food poses a severe clinical and diagnostic problem. Sera were taken from 21 adult patients allergic to birch pollen with symptoms after ingestion of apples, carrots and celeries, and seven control subjects allergic to birch pollen only. Concentrations of allergen-specific IgE against allergens of birch pollen, apple, carrot and celery were measured with enzyme immunoassay, fluorimetric enzyme-linked immunoassay and immunoblotting. Immunoblotting technique may serve as a valuable diagnostic tool for birch pollen associated cross-reactivity.     

Upregulation of nasal mucosal eotaxin in patients with allergic rhinitis during grass pollen season: effect of a local glucocorticoid

BACKGROUND: Allergic rhinitis is a common disease characterized by infiltration of eosinophils into the nasal mucosa during the periods of symptoms. Among chemokines, which attract cells to the site of inflammation, eotaxin is relatively specific for eosinophils. OBJECTIVE: We examined the influence of grass pollen season on nasal eotaxin expression in patients with seasonal allergic rhinitis, as well as the effect of a nasal glucocorticoid on this eotaxin expression. METHODS: Nineteen patients with allergic rhinitis received treatment with either nasal beclomethasone (400 microgram/day) or placebo over a grass pollen season. In these patients, nasal biopsies were taken prior to and during the peak of the pollen season and stained immunohistochemically for eotaxin and EG2 + eosinophils. Five healthy subjects served as controls and gave nasal biopsies once prior to the pollen season. RESULTS: Prior to pollen season, there was no significant difference in nasal eotaxin expression between patients with allergic rhinitis and healthy subjects. Grass pollen season induced significant increase in eotaxin expression in placebo-treated (P = 0.04; n = 9) but not in beclomethasone-treated rhinitis patients (P = 0.8; n = 10). During peak grass pollen season, the eotaxin expression in placebo-treated patients was significantly higher compared with healthy subjects outside season (P = 0.03). There was no significant correlation between the expression of eotaxin and the number of EG2 + eosinophils in nasal mucosa. The serum levels of eotaxin in rhinitis patients remained stable over the pollen season. CONCLUSION: Expression of eotaxin in nasal mucosa of grass-pollen allergic rhinitis patients is upregulated during pollen season and treatment with a nasal glucocorticoid protects against this upregulation.     

Ragweed-specific IgA in nasal lavage fluid of ragweed-sensitive allergic rhinitis patients: increase during the pollen season

Because the secretions of asthma and rhinitis contain toxic eosinophil granule proteins and because secretory IgA is the most potent immunoglobulin stimulus for eosinophil degranulation, we measured eosinophil-derived neurotoxin and ragweed-specific IgA and IgE antibodies in nasal lavage before and during the ragweed pollen season in 44 hay fever patients. We found IgA antibody in nanogram/milliliter concentrations before the season and rising 20-fold by the end of the season. IgE antibody was present in picogram/milliliter concentrations and did not change. Eosinophils and eosinophil-derived neurotoxin also increased. We conclude that IgA is the predominant antibody in allergic nasal secretions and increases with allergen exposure. The hypothesis that secretory IgA antibody-allergen complexes contributes to allergic inflammation by stimulating eosinophil degranulation warrants further study.     

Efficacy of injection immunotherapy with ragweed and birch pollen in elderly patients

BACKGROUND: The role of specific immunotherapy (SIT) in elderly allergic patients is still debated. OBJECTIVE: The aim of this study was to assess whether SIT is associated with a better control of symptoms and a better quality of life also in older allergic patients. METHODS: The effect of injection SIT was assessed in 39 patients [age >54 years, median 59; 29 patients (74%) with asthma, otherwise healthy] monosensitized to birch (n = 20) and ragweed (n = 19). Thirty-three younger subjects [age <50 years, median 35; 26 patients (79%) with asthma, otherwise healthy] monosensitized to birch (n = 10) and ragweed (n = 23), and 37 subjects >54 years old (25 males/12 females; age 55-79 years, median 59 years) monosensitized to birch (n = 18) and ragweed (n = 19) who refused to undergo SIT were enrolled as positive and negative controls, respectively. All groups had a disease duration <10 years; the disease was inadequately controlled with standard drug therapies in all cases. SIT was carried out using the same extracts and was administered using a perennial schedule both in patients and controls. Seasonal therapies were the same in all groups and were not changed after SIT was started. After 1-5 years of SIT, patients and controls were asked to quantify symptom reduction on a visual analogue scale: reductions >50% were considered significant. Moreover, the use of cetirizine and/or salbutamol as an adjunct to standard therapies during the last pollen season was assessed as an objective measure of SIT outcome. RESULTS: 37/39 (95%) patients versus 32/33 (97%) controls submitted to SIT reported a symptom reduction >50% after 1-5 years of SIT (nonsignificant). The median clinical efficacy of SIT was 80% in both groups (nonsignificant). 27/37 controls not submitted to SIT did not report any change in symptom severity at the follow-up visits, whereas 10/37 reported a more severe disease (4 subjects reported the appearance of seasonal asthma) (p < 0.001 vs. patients submitted to SIT). Patients used less frequently cetirizine (p < 0.001) and/or salbutamol (p < 0.05) than controls not submitted to SIT. CONCLUSION: Injection SIT can be considered an effective therapeutic option in otherwise healthy elderly patients with a short disease duration whose symptoms cannot be adequately controlled by drug therapies alone.     

Eosinophil chemotactic activity in Leishmania amazonensis promastigotes

 Tissue eosinophilia was observed in the subcutaneous tissue of mice shortly after their inoculation not only with living but also with lysed promastigotes of Leishmania amazonensis. Intraperitoneal inoculation of lysed promastigotes from five different Leishmania species (L. donovani, L. chagasi, L. tropica, L. amazonensis, and L. braziliensis) induced eosinophil accumulation in the mouse peritoneum. This eosinophil infiltration was also detected in C5-deficient AKR mice, indicating complement independent eosinophil chemotaxis by the parasite. The induced eosinophils were hypodense, suggesting activation of the cells. Finally, we demonstrated in vitro eosinophil chemotactic activity in the promastigote lysates using purified eosinophils and blind well chambers. These results suggest the presence of an eosinophil chemotactic factor in Leishmania, a protozoan parasite. Received: 6 November 1995 / Accepted: 31 January 1996     

The formation of eosinophil and neutrophil chemotactic activity during a pollen season and after allergen challenge

Heat-stable (HS) and heat-labile (HL) neutrophil chemotactic activities (NCAs) have been demonstrated in serum after allergen challenge of subjects with asthma. In this investigation, we have studied the possible occurrence of similar activities in 20 atopic individuals on natural exposure to allergen, that is, during the birch-pollen season. Since eosinophil accumulation is a hallmark of an ongoing allergic inflammation in the respiratory tract also, the possible production of eosinophil chemotactic activity (ECA) was examined in serum after allergen challenge and at natural exposure to pollen. Both HL-NCA and HL-ECA were produced to a significant extent (p less than 0.001) during the season, with the peak of activities occurring simultaneously with the peak pollen count. HL-ECA was produced after allergen challenge of subjects with asthma in the laboratory, as has been demonstrated for NCA previously. The activity of the HS-NCA was unaltered during season. Gel-filtration studies of the major HL-NCA and HL-ECA indicated a molecular weight for both activities of 100 to 150,000, and the activities produced during season cochromatographed with the HL-NCA and HL-ECA produced after allergen challenge in the laboratory, suggesting that all these activities are due to one and the same molecule. The results suggest that the heat-labile chemotactic activity found in serum of atopic subjects and subjects with asthma after allergen exposure may be involved in the attraction of eosinophils and neutrophils to the site of allergic inflammation.     

The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure

Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT-treated group. Also, the EOS cationic protein levels were raised in the non-IT-treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT-treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment.     

Nasal reactivity to capsaicin in patients with seasonal allergic rhinitis during and after the pollen season

BACKGROUND: We aimed to study the participation of neurogenic mechanisms in nasal allergic inflammation by assessing the effect of neurogenic stimulation on the secretory and cellular responses of nasal mucosa in patients with allergic rhinitis. METHODS: A group of patients suffering from seasonal allergic rhinitis was challenged intranasally with incremental doses of capsaicin (0.3, 3, 12 microg) during and after the pollen season. Clinical symptoms after provocations were monitored, and unilateral nasal lavages were obtained. The nasal lavage fluid (NAL) was assayed for concentration of total protein, albumin, lactoferrin, and number of leukocytes, following by differential count. RESULTS: Capsaicin challenge during the pollen season produced greater congestion (P < 0.01) and rhinorrhea (P < 0.05) than after the season. The intensity of burning sensation (pain) was similar on both occasions. Capsaicin failed to increase albumin content in NAL both during and after the season. Total protein was increased only after the highest dose of capsaicin (P < 0.03) after the season. The number of eosinophils in basal lavages was higher during the season. During the season, the total number of leukocytes at least doubled in 7/12 patients and the percentage of eosinophils increased in 6/12 patients after the capsaicin challenge. CONCLUSIONS: Our study demonstrated that during the symptomatic period the nasal mucosa of allergic patients is more susceptible to neurogenic stimulation, showing enhanced secretory and inflammatory (cellular) responses.     

The nasal response to histamine challenge: effect of the pollen season and immunotherapy.

To evaluate changes in the nasal response to histamine, we challenged 19 subjects with allergic rhinitis caused by ragweed (RW) before, during, and after the RW season with increasing doses of histamine diphosphate. We compared their response, as measured by symptoms and the levels of TAME-esterase activity and albumin recovered in the nasal lavage fluid, with response of two groups with allergic rhinitis undergoing immunotherapy with moderate-dose (N = 16) and high-dose (N = 11) RW (2 and 24 micrograms of antigen E [Amb a I] as maintenance dose, respectively). Four challenges with histamine were performed in each group: before, at the peak of, near the end of, and 2 weeks after the RW season. The three groups of subjects had similar skin sensitivity to antigen and levels of TAME-esterase activity and albumin recovered from nasal lavages after histamine challenge performed before seasonal exposure. Symptom diaries obtained throughout the season revealed a significant reduction only in the high-dose immunotherapy-treated group. At the peak of the season, the untreated group had more symptoms in response to the challenge compared with the challenges before and after the season (p = 0.04 for both groups). The saline challenge occurring before challenging with histamine also demonstrated a significant increase at the peak of the season compared with increases before the season (p = 0.02). This observation was also true for the levels of albumin and TAME-esterase activity. If the response after saline challenge was subtracted from each response after histamine challenge, no difference was found in the results between any of the visits.(ABSTRACT TRUNCATED AT 250 WORDS)