Airway angiogenesis in patients with rhinitis and controlled asthma

Background Airway angiogenesis may be an important part of structural remodelling in the pathogenesis of asthma. The development of asthma is frequently preceded by rhinitis.
Objective We sought to determine whether the levels of angiogenesis-related factors are elevated in airways of patients with rhinitis or controlled asthma.
Methods We analysed the induced sputum of 18 rhinitis patients, 16 asthmatic patients, and 15 healthy controls. The concentrations of angiogenin, vascular endothelial growth factor (VEGF), IL-8, fibroblast growth factor (bFGF), and TNF-α were measured by cytometric bead arrays.
Results We found significantly increased angiogenin and VEGF concentrations in the induced sputum supernatant of both rhinitis and asthma patients compared with that of the healthy control group ( P 0.0005). With the exception of TNF-α, there was no difference in the other angiogenic factors; TNF-α levels were higher in the rhinitis group than in the control group ( P =0.02).
Conclusion These in vivo results suggest increased airway angiogenesis in patients with rhinitis without asthma as well as in corticosteroid-treated and well-controlled asthma patients.     

Occupational rhinitis

The present document is the result of a consensus reached by a panel of experts from European and nonEuropean countries on Occupational Rhinitis (OR), a disease of emerging relevance, which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored to that of occupational asthma, as well as a diagnostic algorithm based on steps allowing different levels of diagnostic evidence, are proposed. The needs for future research are pointed out. Key messages are issued for each item.     

Nasal response in subjects undergoing challenges by inhaling occupational agents causing asthma through the nose and mouth

Background Subjects with occupational asthma (OA) often report nasal symptoms, but nasal reactions to inhalation challenges with occupational agents have not been well characterized. Methods Fifteen subjects with OA (eight due to high-molecular-weight agents - flour and guar gum - and seven due to isocyanates) underwent inhalational challenges using closed-circuit devices (dry particles for high-molecular-weight agents and gas generator for isocyanates) on two occasions, 2-4 weeks apart in a random fashion. On one occasion, they inhaled through the nose and, on another, through the mouth. The FEV, was monitored for up to 8 h afterward, and symptoms were documented with a standardized questionnaire on nasal symptomatology, assessment of nasal resistance by rhinomanometry, and nasal lavage for the examination of cells and mediators. Results Inhaling through the mouth and through the nose:

• 1) yielded similar asthmatic responses (25 ± 8% and 22 ± 10% maximum changes in FEV₁)
• 2) more than doubled the peak nasal symptoms and nasal resistance when the maximum daily response was compared with prechallenge results.

This increase occurred on the days of inhalational challenges through the mouth and through the nose. There were some significant responses assessed by nasal lavage in terms of cells and mediators, again with no differences between the days of challenges through the mouth and through the nose. Conclusions Inhaling occupational agents of high or low molecular weight, including isocyanates, whether through the mouth or nose:

• 1) results in a similar asthmatic response
• 2) causes a significant nasal response in terms of symptoms and an increase n i nasal resistance
• 3) causes some significant changes in inflammatory cells and mediators.

     

Lower airway inflammatory responses to repeated very-low-dose allergen challenge in allergic rhinitis and asthma

BACKGROUND: Low-dose allergen challenge (LDAC) may be a useful tool for studying the capacity of allergens to induce airway inflammation in atopic subjects. OBJECTIVE: To evaluate lower airway inflammatory changes following repeated inhalation of very low doses of allergen (VLDAC) in non-asthmatic subjects with allergic rhinitis (NAAR) compared with mild allergic asthmatic subjects (AA). METHODS: Fourteen NAAR and 11 AA were seen out of the pollen season and had skin prick tests with common aeroallergens. Baseline spirometry (S) and methacholine challenge (MC) were done and blood and induced sputum (IS) differential cell counts were obtained. Each subject underwent VLDAC on four consecutive mornings with a relevant allergen. S, MC, and blood and IS samplings were repeated 6 h after the second and fourth VLDAC and one week later. RESULTS: Although there were, as expected, no changes in FEV1 or PC20 in either group, mean percentage eosinophils on IS were significantly increased in NAAR on day 2 of VLDAC and decreased in all but one subject on day 4, with a tendency to return to baseline levels one week later. In AA, there was a non-significant trend for sputum eosinophils to increase on day 2; four subjects showed a decrease of eosinophils on day 4 of VLDAC. There was a correlation between eosinophil cationic protein (ECP) levels and eosinophil counts in NAAR throughout the study. There were no variations in other sputum cells or blood inflammatory cells. CONCLUSION: VLDAC can increase the percentage of eosinophils in IS of NAAR subjects without associated respiratory symptoms nor physiological modifications. A reduction in eosinophilic response despite repeated exposure, more common in NAAR subjects, suggests an adaptation process that needs to be further evaluated.     

Sputum eosinophilia: an early marker of bronchial response to occupational agents

Background: False‐negative responses to specific inhalation challenge (SIC) with occupational agents may occur. We explored whether assessing changes in sputum cell counts would help improve the identification of bronchial reactivity to occupational agents during SICs. Methods: The predictive value of the changes in sputum cell counts after a negative FEV₁ response to a first challenge exposure to an occupational agent was determined using the changes in airway calibre observed during repeated challenges as the ‘gold standard’. The study included 68 subjects investigated for work‐related asthma in a tertiary centre. After a control day, the subjects were challenged with the suspected occupational agent(s) for up to 2 h. All subjects who did not show an asthmatic reaction were re‐challenged on the following day. Additional challenges were proposed to those who demonstrated a ≥ 2% increase in sputum eosinophils or an increase in nonspecific bronchial hyperresponsiveness to histamine after the second challenge day. Results: Six of the 35 subjects without changes in FEV₁ on the first challenge developed an asthmatic reaction on subsequent challenges. ROC analysis revealed that a >3% increase in sputum eosinophils at the end of the first challenge day was the most accurate parameter for predicting the development of an asthmatic response on subsequent challenges with a sensitivity of 67% and a specificity of 97%. Conclusions: An increase in sputum eosinophils is an early marker of specific bronchial reactivity to occupational agents, which may help to identify subjects who will develop an asthmatic reaction only after repeated exposure.     

Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma

BACKGROUND: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma. METHODS: A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. RESULTS: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.     

Occupational asthma and rhinitis due to glutaraldehyde: changes in nasal lavage fluid after specific inhalatory challenge test

BACKGROUNDd: Glutaraldehyde (GA) is a known respiratory sensitizers, and some studies have reported occupational asthma in exposed workers. Specific changes in nasal lavage fluid (NLF) induced by high-molecular-weight allergen provocation in sensitized subjects were described previously. The purpose of this study was to evaluate the changes in cytogram, protein content, eosinophil cationic protein (ECP), and mast-cell tryptase concentrations in NLF after GA inhalation challenge in patients with a positive history of GA-induced asthma and late or dual asthmatic response due to exposure to low-level GA. METHODS: A single-blind, placebo-controlled study was performed on 11 health workers with occupational asthma and rhinitis due to GA. The control groups comprised 10 atopic subjects with perennial asthma and rhinitis and 10 healthy ones. A "nasal pool" technique was used to evaluate the examined parameters in nasal washings before and 30 min, 4 h, and 24 h after the inhalatory provocation with GA and placebo. RESULTS: There was a significant increase in eosinophil number and percentage, and albumin, ECP, and tryptase concentrations in NLF from patients with occupational asthma and rhinitis when compared to controls. CONCLUSIONS: The results indicate the immunologic mechanism of GA-induced asthma and the applicability of the "nasal pool" technique as the diagnostic procedure in GA-induced airway allergy.     

Links between rhinitis and asthma

There is compelling evidence of a close relationship between the upper and lower airways in asthma and rhinitis. Rhinitis is present in the majority of patients with asthma, and a significant minority of patients with rhinitis have concomitant asthma. Similarities between the two conditions occur in the nature of the inflammation present in the target tissues. A common initiating step in the inflammatory process of allergic airways disease is the presence of immunoglobulin E providing an adaptor molecule between the offending allergen and inflammatory cell activation and mediator release. Differences in the two conditions arise largely from the structural differences between the nose and the lungs. In an asthmatic, concomitant allergic rhinitis increases healthcare costs and further impairs quality of life. The presence of rhinitis should always be investigated in children and young adults with asthma. Subjects with allergic rhinitis have an increased risk of developing asthma and may form a suitable population for secondary intervention to interrupt the 'allergic march'.     

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.     

The CX3C chemokine fractalkine in allergic asthma and rhinitis

BACKGROUND: Unlike other chemokines, fractalkine is expressed as a membrane-bound form, mainly on endothelial and epithelial cells, and can be shed as a soluble chemotactic form. Fractalkine can capture leukocytes expressing its receptor (CX(3)CR(1)), including T lymphocytes, rapidly and firmly in an integrin-independent manner. Because of its dual activity, fractalkine plays a major role in the transendothelial and transepithelial migration of leukocytes during inflammation. OBJECTIVE: We sought to study the fractalkine-CX(3)CR(1) axis in patients with allergic airways diseases. METHODS: Plasma fractalkine levels were measured by means of ELISA in 19 control subjects and 55 patients with symptomatic allergic rhinitis, asthma, or both, and CX(3)CR(1) function was studied by using triple-color flow cytometry in circulating T-lymphocyte subpopulations. Segmental allergen challenge was performed in 16 allergic asthmatic patients to analyze fractalkine expression and inflammatory cell recruitment in bronchoalveolar lavage fluid and bronchial biopsy specimens. RESULTS: Compared with control subjects, patients with symptomatic allergic rhinitis and asthmatic patients had increased circulating fractalkine levels, and CX(3)CR(1) function was upregulated in circulating CD4(+) T lymphocytes. Twenty-four hours after segmental allergen challenge, bronchoalveolar lavage fluid soluble fractalkine concentrations increased and correlated with the total number of recruited cells. Bronchial epithelial and endothelial cells expressed high levels of the membrane-bound form of fractalkine before and after challenge. CONCLUSION: Allergic asthma and rhinitis are associated with systemic and bronchial upregulation of the chemotactic axis fractalkine-CX(3)CR(1). This might contribute to the rapid recruitment of circulating CD4(+) T lymphocytes in the airways after allergen stimulation.     

Comparison of biomarkers between allergic rhinitis only and allergic rhinitis with concomitant asthma

This post hoc analysis suggests distinct immunologic profiles in the allergic rhinitis (AR)‐only and the AR & AA phenotypes.