Serum surfactant protein D is elevated in allergic patients.

BACKGROUND: There is evidence that surfactant protein (SP)-D is important in the innate, as well as in the adaptive pulmonary immune response. Serum concentrations of SP-D have been proposed as parameter of the integrity of the blood-airspace barrier in interstitial lung diseases. We hypothesized that serum SP-D concentrations are affected in allergic patients and correlate with changes in allergic airway inflammation. OBJECTIVE: To determine levels of serum SP-D in allergic patients compared with non-allergic controls. Furthermore, to investigate associations between serum SP-D concentrations on the one hand and changes in commonly used markers of bronchial inflammation in allergic airways disease on the other hand. MATERIALS AND METHODS: Fifty allergic patients were studied and bronchial allergen challenge was used as a model to increase bronchial allergic inflammation in these patients. Serum SP-D concentrations, inflammatory parameters in induced sputum and bronchial hyper-responsiveness (BHR) were determined before and after allergen challenge. Twenty-five non-allergic volunteers served as controls. RESULTS: Baseline serum SP-D was significantly higher in allergic patients as compared with controls (mean serum SP-D concentration (95% confidence interval): 62.7 (55.5, 70.0) in allergic patients vs. 49.5 (36.7, 62.3) ng/mL in non-allergic controls, P=0.006). In addition, baseline serum SP-D appeared to be an independent predictor for the magnitude of the late asthmatic response after allergen challenge. Furthermore, serum SP-D was predictive for the sputum eosinophil cationic protein concentration after allergen challenge. CONCLUSION: We propose that serum SP-D concentrations are associated with allergic bronchial inflammation and may give additional information, beside BHR and sputum eosinophils, about the degree of bronchial inflammation in allergic patients.

Similar levels of nitric oxide in exhaled air in non-asthmatic rhinitis and asthma after bronchial allergen challenge.

BACKGROUND: Nitric oxide in exhaled air (eNO) is elevated in allergic asthma compared with healthy subjects and has been proposed as a marker of bronchial inflammation. However, eNO is elevated to a lesser extent in allergic non-asthmatic rhinitis as well. Considering the distinctive clinical appearances of both allergic diseases, differences in eNO are expected to persist after allergen exposure. The aim of the study was to compare allergen-induced changes in eNO in house dust mite sensitized patients with asthma and patients with perennial rhinitis without asthma symptoms. METHODS: Bronchial allergen challenge was performed in 52 patients sensitized to house dust mite (Dermatophagoides pteronyssinus), of whom 26 had non-asthmatic rhinitis and 26 had asthma. Levels of eNO were measured before and 1 h, 1 day and 1 week after challenge. RESULTS: At baseline eNO was significantly lower in non-asthmatic rhinitis compared with asthma (geometric mean eNO (SEM): 121 (1.1) in non-asthmatic rhinitis vs 197 (1.1) nl/min in asthma, P < 0.006). However, the increase in eNO after bronchial allergen challenge in non-asthmatic rhinitis, in particular in those patients with a dual asthmatic response, significantly exceeded the increase in asthma resulting in similar levels of eNO after challenge (geometric mean eNO (SEM) at 24 h postchallenge 204 (1.1) in non-asthmatic rhinitis vs 244 (1.1)nl/min in asthma, P = 0.3). CONCLUSION: The difference in eNO between non-asthmatic rhinitis and asthma at baseline is abolished after allergen exposure due to a significantly greater increase in eNO in non-asthmatic rhinitis.

Allergen-induced bronchial inflammation in house dust mite-allergic patients with or without asthma.

BACKGROUND: It is presently unknown which factors determine the occurrence and persistence of asthma in house dust mite-allergic individuals. The level of allergen-specific IgE antibodies does not seem to be decisive for asthmatic symptoms. Moreover, levels of exposure to mite allergens do not seem to differ significantly between asthmatic and non-asthmatics individuals. AIM: It was hypothesized that the presence or absence of asthmatic symptoms in house dust mite-allergic patients is associated with quantitative or qualitative differences in the cellular bronchial inflammatory response during the late phase of the allergic reaction. This hypothesis was tested in the bronchial allergen challenge model. MATERIAL AND METHODS: Whole lung challenges with house dust mite extract were performed in 52 house dust mite-allergic subjects, of whom 26 had asthma and 26 had perennial rhinitis without asthmatic symptoms. Primary outcomes were parameters for bronchial inflammation in serial samples of induced sputum (cell differentials, eosinophil cationic protein (ECP), interleukin-8 (IL-8), myeloperoxydase (MPO)). In addition, lung function, non-specific bronchial hyper-responsiveness and serial blood samples (eosinophils and IL-5) were analysed. RESULTS: At baseline sputum eosinophils and ECP were similar in both groups but neutrophils and IL-8 were higher in asthmatics. The early bronchoconstriction after allergen challenge was similar in asthma and non-asthmatic rhinitis (median decrease in FEV1: asthma -31.7% vs. non-asthmatics -29.1%, P > 0.1). The late phase bronchoconstriction was significantly greater in asthma (median decrease in FEV1: asthma -27.6% vs. non-asthmatics -18.9%, P = 0.02). Induction of bronchial hyper-responsiveness was similar in both groups. Bronchial allergen challenge elicited significant increases in sputum eosinophils and ECP, which were indistinguishable for both groups (P > 0.1 and P = 0.07, respectively). In contrast, higher numbers of neutrophils persisted in asthma 24h after challenge and were accompanied by significant increases in IL-8 and MPO, which were absent in non-asthmatics (difference between groups P = 0.007 and P = 0.05, respectively). CONCLUSION: Allergen challenge inducedvery similar increases in eosinophils and ECP in induced sputum in allergic asthmatics and in allergic non-asthmatic patients. The difference in bronchial inflammation between asthma and non-asthmatic rhinitis appeared to be more closely related to indices for neutrophilic inflammation.

The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren.

BACKGROUND: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. METHODS: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. RESULTS: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. CONCLUSIONS: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.

Atopy, lung function, and obstructive airways disease after prenatal exposure to famine.

BACKGROUND: Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. METHODS: Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). RESULTS: Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0. 9 to 2.6). CONCLUSIONS: The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.

Bronchial allergen challenge with isolated major allergens of Dermatophagoides pteronyssinus: the role of patient characteristics in the early asthmatic response.

BACKGROUND: The use of allergen extracts will hamper studies into quantitative aspects of allergic responses because the precise amount of relevant allergen for each patient is unknown. OBJECTIVE: We applied isolated IgE-binding components (major allergens) in the technique of bronchial allergen challenge to determine the role of patient characteristics in the early asthmatic response (EAR). METHODS: In 30 patients with mild-to-moderate asthma, the EAR was investigated after inhalation of an isolated major allergen of Dermatophagoides pteronyssinus (i.e., Der p 1 [n = 16] or Der p 2 [n = 14]). The degree of early-phase bronchial responsiveness to allergen (the cumulated dose of allergen causing a 20% fall in FEV1 [PD20allergen]) was related to the degree of nonspecific bronchial responsiveness (the concentration of histamine causing a 20% fall in FEV1 [PC20histamine]) and the level of specific IgE or allergen thresholds as found in skin tests and basophil histamine release assays. RESULTS: Twenty-seven patients with an immediate response during allergen and histamine challenges (deltaFEV1, > or = 20%) were analyzed. In these patients, a strong correlation was found between PD20allergen and PC20histamine (r = 0.81, p < 0.001). Weak correlations were found between PD20allergen and the level of specific IgE (r = -0.36, p = 0.07) or allergen thresholds as found in skin tests (skin prick test, r = 0.36 and p = 0.07; intracutaneous test, r = 0.49 and p = 0.01) or basophil histamine release assays (r = 0.37, p = 0.08). Moreover, no significant contribution of these indices of IgE-mediated hypersensitivity to the prediction of PD20allergen by multilinear regression models with PC20histamine was found. CONCLUSION: In asthmatic patients allergic to house dust mites the degree of nonspecific bronchial hyperresponsiveness is the main determinant of early-phase bronchial responsiveness to allergen. In these patients the degree of allergic sensitivity does not contribute to the prediction of the EAR after allergen inhalation.