Sergio Bonini

Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study

Abstract Objective: To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. Design: Retrospective case-control study. Participants: 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. Setting: Air force school in Caserta, Italy. Main outcome measures: Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis. Results: Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18%v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0.70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). Conclusion: Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.

Allergenic pollen and pollen allergy in Europe

The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas.

Vernal keratoconjunctivitis revisited: A case series of 195 patients with long-term followup

OBJECTIVE This study aimed at revisiting vernal keratoconjunctivitis (VKC) on the basis of anamnestic, clinical, immunologic, histopathologic, and followup data of 195 patients. DESIGN Retrospective noncomparative case series. PARTICIPANTS One hundred and ninety-five patients with VKC. METHODS Clinical evaluation and outcome in 151 of 195 patients with a median followup of 47 months. Evaluation was by telephone survey in 69 patients. MAIN OUTCOME MEASURES (1) Demographic, clinical, and immunologic features of VKC and their influence on the course of the disease; (2) conjunctival and corneal complications and efficacy of treatment observed during the followup period. RESULTS VKC is a chronic disease. More than 60% of patients had repeated recurrences all year round. Males had an earlier presentation of symptoms than females and the male/female ratio decreased with age. Major (greater than 80%) and minor (up to 80%) diagnostic criteria were defined for clinical signs and symptoms of the disease. Negative skin test or radioallergosorbent test was present in approximately 50% of patients, whereas eosinophil infiltration was a constant histopathologic finding. A marked conjunctival sensitivity to nonspecific stimuli was noted in more than one third of patients. In 6% of cases, a reduction of visual acuity resulted from corneal scarring, and in 2% of patients, steroid-induced glaucoma was observed. The large size of giant papillae indicates poor prognosis for the persistence of the disease and its evolution into a chronic, perennial condition. CONCLUSIONS VKC is a chronic eosinophilic disease of the ocular surface involving IgE, non IgE-mediated mechanisms, and age-sex-related influences. Although the disease has a good prognosis, severe visual impairments may result from long-standing inflammation.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008

J. Bousquet, N. Khaltaev, A. A. Cruz, J. Denburg, W. J. Fokkens, A. Togias, T. Zuberbier, C. E. Baena-Cagnani, G. W. Canonica, C. van Weel, I. Agache, N. A t-Khaled, C. Bachert, M. S. Blaiss, S. Bonini, L.-P. Boulet, P.-J. Bousquet, P. Camargos, K.-H. Carlsen, Y. Chen, A. Custovic, R. Dahl, P. Demoly, H. Douagui, S. R. Durham, R. Gerth van Wijk, O. Kalayci, M. A. Kaliner, Y.-Y. Kim, M. L. Kowalski, P. Kuna, L. T. T. Le, C. Lemiere, J. Li, R. F. Lockey, S. Mavale-Manuel , E. O. Meltzer, Y. Mohammad, J. Mullol, R. Naclerio, R. E. O Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. A. Popov, K. F. Rabe, J. Rosado-Pinto, G. K. Scadding, F. E. R. Simons, E. Toskala, E. Valovirta, P. van Cauwenberge, D.-Y. Wang, M. Wickman, B. P. Yawn, A. Yorgancioglu, O. M. Yusuf, H. Zar Review Group: I. Annesi-Maesano, E. D. Bateman, A. Ben Kheder, D. A. Boakye, J. Bouchard, P. Burney, W. W. Busse, M. Chan-Yeung, N. H. Chavannes, A. Chuchalin, W. K. Dolen, R. Emuzyte, L. Grouse, M. Humbert, C. Jackson, S. L. Johnston, P. K. Keith, J. P. Kemp, J.-M. Klossek, D. Larenas-Linnemann, B. Lipworth, J.-L. Malo, G. D. Marshall, C. Naspitz, K. Nekam, B. Niggemann, E. Nizankowska-Mogilnicka, Y. Okamoto, M. P. Orru, P. Potter, D. Price, S. W. Stoloff, O. Vandenplas, G. Viegi, D. Williams

Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair

Nerve growth factor (NGF) is a polypeptide which, in addition to its effect on nerve cells, is believed to play a role in inflammatory responses and in tissue repair. Because fibroblasts represent the main target and effector cells in these processes, to investigate whether NGF is involved in lung and skin tissue repair, we studied the effect of NGF on fibroblast migration, proliferation, collagen metabolism, modulation into myofibroblasts, and contraction of collagen gel. Both skin and lung fibroblasts were found to produce NGF and to express tyrosine kinase receptor (trkA) under basal conditions, whereas the low-affinity p75 receptor was expressed only after prolonged NGF exposure. NGF significantly induced skin and lung fibroblast migration in an in vitro model of wounded fibroblast and skin migration in Boyden chambers. Nevertheless NGF did not influence either skin or lung fibroblast proliferation, collagen production, or metalloproteinase production or activation. In contrast, culture of both lung and skin fibroblasts with NGF modulated their phenotype into myofibroblasts. Moreover, addition of NGF to both fibroblast types embedded in collagen gel increased their contraction. Fibrotic human lung or skin tissues displayed immunoreactivity for NGF, trkA, and p75. These data show a direct pro-fibrogenic effect of NGF on skin and lung fibroblasts and therefore indicate a role for NGF in tissue repair and fibrosis.

Human CD4+ T cell clones produce and release nerve growth factor and express high-affinity nerve growth factor receptors

BACKGROUND Increasing evidence shows that nerve growth factor (NGF) plays a role in the complex and fascinating linkage between the nervous and the immune systems due to its ability to modulate functions of several inflammatory cells. OBJECTIVE To investigate NGF receptor expression and NGF production and release by human CD4+ cells clones, which have primary relevance in modulating inflammatory events through their different subsets of functional phenotypes. METHODS The expression of NGF and a transmembrane tyrosine kinase (TrkA) was evaluated by immunohistochemistry and flow cytometry analysis in five T(H0), six T(H1), and five T(H2) cell clones derived from human circulating mononuclear blood cells. Moreover, the amount of NGF protein was assessed by measuring the NGF levels in culture supernatants of the T cell clones before stimulation and 48 hours after phytohemagglutinin (PHA) activation by use of an immunoenzymatic assay. RESULTS Our data have shown that in unstimulated conditions, human CD4+ T cell clones express both immunoreactivity for NGF and the TrkA NGF receptor irrespective of their cytokine profile. Moreover, T(H1) and T(H2) clones, but not T(H0) clones, secrete NGF in basal conditions. PHA activation induces NGF secretion in T(H0) clones and a significant increase of NGF levels in T(H2) (p < 0.05), but not in T(H1) culture supernatants. CONCLUSIONS Results obtained represent the first evidence of TrkA expression and NGF production and release in human CD4+ cell clones and suggest a possible functional role of NGF in modulating the immune and inflammatory network.

The expanding role of nerve growth factor : from neurotrophic activity to immunologic diseases

Numerous studies published in the last 10–15 years have shown that nerve growth factor (NGF), a polypeptide originally discovered in connection with its neurotrophic activity, also acts on cells of the immune system. NGF has been found in various immune organs including the spleen, lymph nodes, and thymus, and cells such as mast cells, eosinophils, and B and T cells. The circulating levels of NGF increase in inflammatory responses, in various autoimmune diseases, in parasitic infections, and in allergic diseases. Stress‐related events both in animal models and in man also result in an increase of NGF, suggesting that this molecule is involved in neuroendocrine functions. The rapid release of NGF is part of an alerting signal in response to either psychologically stressful or anxiogenic conditions in response to homeostatic alteration. Thus, the inflammation and stress‐induced increase in NGF might alone or in association with other biologic mediators induce the activation of immune cells during immunologic insults. A clearer understanding of the role of NGF in these events may be useful to identify the mechanisms implicated in certain neuroimmune and immune dysfunctions.

Nerve growth factor is preformed in and activates human peripheral blood eosinophils

BACKGROUND Recent studies have shown that nerve growth factor (NGF) is produced by and can act on several immune-inflammatory cells. OBJECTIVES The objective of this study was to study the effects of NGF on human peripheral blood eosinophils and assess whether these cells produce and store NGF. METHODS Eosinophils were purified by negative immunoselection (magnetic cell sorting systems, purity 98% to 100%) from 13 subjects (9 to 26 years old) with mild blood eosinophilia, mainly of allergic origin. Eosinophils were incubated with NGF (50 to 1000 ng/mL), and supernatants were collected for measurement of eosinophil peroxidase (EPO, 20 minutes, colorimetric enzymatic assay) and IL-6 (12 hours, ELISA). Eosinophil viability was evaluated by Trypan blue test (days 2, 3, and 4). NGF content in freshly isolated eosinophils, after ultrasound disruption, was determined with a 2-site immunoenzymatic assay. The presence of mRNA for NGF was evaluated by reverse transcription PCR. RESULTS NGF caused EPO release (highly significant at 1000 ng/mL NGF). IL-6 release from eosinophils was not higher than IL-6 spontaneously released into culture medium alone. NGF did not significantly affect the number of viable eosinophils. NGF was found in the eosinophil sonicates (1.5 to 17.8 pg/mL per 106 cells). Similarly, mRNA for NGF was detected by reverse transcription PCR in the freshly isolated eosinophils. CONCLUSIONS NGF activates human peripheral blood eosinophils from subjects with mild eosinophilia to selectively release inflammatory mediators. Eosinophils store and produce NGF. Therefore the capability of NGF to induce a secretory response and its production and storage by circulating human eosinophils suggest a possible role for NGF in conditions associated with eosinophilia, including allergic disease.

Standard skin prick testing and sensitization to inhalant allergens across Europe--a survey from the GALEN network

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan‐European core SPT panel.

Studies on the relationship between the level of specific IgE antibodies and the clinical expression of allergy: I. Definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens

BACKGROUND The detection of specific IgE antibodies to environmental allergens does not always coincide with a diagnosis of clinically evident allergic disease, because some patients with positive skin and/or in vitro test results have no symptoms related to the allergen or allergens that induced the antibodies. OBJECTIVE In a multicenter study the optimal cutoff values for specific IgE antibody levels and skin test results that could discriminate between patients with symptomatic and those with asymptomatic allergy were determined. METHODS IgE antibodies specific for a panel of common aeroallergens were assayed with the Pharmacia CAP System (Pharmacia, Uppsala, Sweden) in two groups of patients, a group of 267 patients with symptomatic allergy and a group of 232 with asymptomatic allergy--both with positive skin prick test results--and in a group of 243 healthy, nonallergic control subjects. The cutoff values were established by receiver operating characteristic analysis. RESULTS A significantly higher mean specific IgE antibody value was found in patients with symptomatic allergy compared with patients with asymptomatic allergy (p < 0.001) and in patients with symptomatic allergy compared with healthy control subjects (p < 0.001). The optimal CAP System cutoff value between patients with symptomatic and those with asymptomatic allergy was 11.7 kU/L, and when seasonal allergens were compared with perennial allergens, the cutoffs were 10.7 kU/L and 8.4 kU/L, respectively. The optimal cutoff value for the skin prick test was a wheel area of 32 mm2 for seasonal allergens and 31 mm2 for perennial allergens. The skin test had a lower diagnostic value (sum of sensitivity and specificity) than the CAP System. CONCLUSIONS Cutoff values for specific serum IgE antibody levels are likely to be useful in clinical practice to distinguish symptomatic from asymptomatic allergy in patients with positive skin test results.