When does a protein become an allergen? Searching for a dynamic definition based on most advanced technology tools

Since the early beginning of allergology as a science considerable efforts have been made by clinicians and researchers to identify and characterize allergic triggers as raw allergenic materials, allergenic sources and tissues, and more recently basic allergenic structures defined as molecules. The last 15–20 years have witnessed many centres focusing on the identification and characterization of allergenic molecules leading to an expanding wealth of knowledge. The need to organize this information leads to the most important question ‘when does a protein become an allergen?’ In this article, I try to address this question by reviewing a few basic concepts of the immunology of IgE-mediated diseases, reporting on the current diagnostic and epidemiological tools used for allergic disease studies and discussing the usefulness of novel biotechnology tools (i.e. proteomics and molecular biology approaches), information technology tools (i.e. Internet-based resources) and microtechnology tools (i.e. proteomic microarray for IgE testing on molecular allergens). A step-wise staging of the identification and characterization process, including bench, clinical and epidemiological aspects, is proposed, in order to classify allergenic molecules dynamically. This proposal reflects the application and use of all the new tools available from current technologies

Cystic Fibrosis, Atopy, Asthma and ABPA

The role of atopy on cystic fibrosis (CF) progression remains unclear but evidence suggests that it may influence the appearance of co-morbid conditions such as CF asthma or allergic bronchopulmonary aspergillosis (ABPA). Recognising asthma in patients with CF is not always easy but the identification of atopic markers favours the diagnosis. Physicians should be aware of this fact in order to achieve a better control of respiratory symptoms in patients with CF. Bronchial mucosa inflammation and abnormal mucus predispose to mould colonisation. These patients are at higher risk of allergic sensitisation, especially when atopic susceptibility is present. In the particular case of A. fumigatus, allergic sensitisation precedes ABPA development, which occurs in up to 10% of CF patients. Progression of lung function deterioration is most strikingly pronounced in patients with ABPA. Therefore, sensitisation with A. fumigatus should be regularly tested in patients with CF, especially those at higher risk. Recombinant allergens constitute an important advance in differentiating Aspergillus sensitisation from ABPA itself

Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. OBJECTIVES: To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.Date of last search of Cochrane trials register: 27 July 2015. SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and risk of bias and extracted data. MAIN RESULTS: We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life. AUTHORS' CONCLUSIONS: The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment

Inhaled corticosteroids for cystic fibrosis

BACKGROUND: Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. Inhaled corticosteroids are being increasingly used to treat children and adults with cystic fibrosis. The rationale for their use is that they have the potential to reduce lung damage arising from inflammation. However chronic use of inhaled steroids may also have adverse effects. It is thus important to establish the current level of evidence about the potential benefits and harms of this practice. OBJECTIVES: The objective of this review is to assess the effectiveness of regular use of inhaled corticosteroids when compared to no inhaled corticosteroids, in the management of patients with cystic fibrosis. SEARCH STRATEGY: Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing inhaled corticosteroids were also contacted to identify any trials of inhaled corticosteroids in cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All trials, both published and unpublished, in which inhaled corticosteroids were compared to either placebo or standard treatment in patients with cystic fibrosis. Trials employing random treatment allocation and those using quasi-random allocation methods such as alternate allocation to treatment and control group were included. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: objective measures of lung function, respiratory exacerbations, use of intravenous antibiotics, hospital admissions, nutritional status, symptoms, quality of life, survival and frequency of adverse effects. Methodological quality of trials was assessed independently using established criteria by two reviewers, who also extracted relevant data independently using standard proformas. Differences were resolved by discussion. MAIN RESULTS: Nine trials were identified reporting the use of inhaled steroids in 266 subjects aged between seven and 45 years with cystic fibrosis. Methodological quality was difficult to assess from published information, specifically with respect to concealment of allocation and method used to generate random sequence. Trials were heterogeneous with respect to inclusion criteria, specifically age, severity of pulmonary involvement, clinical diagnosis of asthma and pulmonary colonisation with Pseudomonas aeruginosa. Trials also differed in type and duration of treatment. Beclomethasone was given for periods of between four and 22 weeks in four trials, budesonide for six weeks and six months respectively in two, and fluticasone for periods of between six weeks and two years in the remaining three. Measures of the volume of air breathed out on a forcible expiration (forced expiratory volumes) were reported in most trials but these data could not be combined for this review partly because reports differed in the way data were summarised and partly because some data were not included in published reports. Outcomes of potentially greater relevance to affected individuals such as nutritional status or quality of life were not reported in any trial. Survival was not reported in any trial, but this may reflect the fact that maximum duration of follow up was too short to allow this outcome to be meaningfully assessed. Adverse effects were systematically documented in only two trials. Although one trial was halted prematurely because a proportion of all those taking part had acquired chronic lung infections with Pseudomonas aeruginosa, no conclusions can be reached from this one small trial as to whether this risk is increased a

Aerosolized Delivery of Antifungal Agents

Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic agents, aerosolized delivery is an attractive option in prevention because the drug can concentrate locally at the site of infection with minimal systemic exposure. Current clinical evidence for the use of aerosolized delivery in preventing fungal infections is limited to amphotericin B products, although itraconazole, voriconazole, and caspofungin are under investigation. Based on conflicting results from clinical trials that evaluated various amphotericin B formulations, the routine use of aerosolized delivery cannot be recommended. Further research with well-designed clinical trials is necessary to elucidate the therapeutic role and risks associated with aerosolized delivery of antifungal agents. This article provides an overview of aerosolized delivery systems, the intrapulmonary pharmacokinetic properties of aerosolized antifungal agents, and key findings from clinical studies

Methyl methacrylate and respiratory sensitization: A Critical review

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer

A pilot study to compare tobramycin 80 mg injectable preparation with 300 mg solution for inhalation in cystic fibrosis patients

BACKGROUND: Inhaled tobramycin has been shown to improve lung function in cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. However, to date no comparative data are available for different dose regimens used in clinical practice