Idiopathic pulmonary fibrosis: an Australian perspective.

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a dismal median survival of 3 years. Patients typically develop progressive dyspnoea and increasing exercise limitation. With a rising incidence and prevalence, an unpredictable disease course and limited treatment options, it is rapidly becoming an important public health concern. To date, lung transplantation has been the sole viable hope for treatment for those who qualify. However, the landscape of idiopathic pulmonary fibrosis management is changing, with the recent emergence of novel pharmacotherapy shown to have a favourable influence on the natural history of this disease.

Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

BACKGROUND: We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. METHODS: A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. RESULTS: Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. CONCLUSIONS: A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.

IgE cross-reactivity between the major peanut allergen Ara h 2 and tree nut allergens.

Allergy to peanut and tree nuts is characterised by a high frequency of life-threatening anaphylactic reactions and typically lifelong persistence. Although peanut is the most common cause of nut allergy, peanut allergic patients are frequently also sensitive to tree nuts. It is not known if this is due to cross-reactivity between peanut and tree nut allergens. In this study, the major peanut allergen Ara h 2 was cloned from peanut cDNA, expressed in E. coli cells as a His-tag fusion protein and purified using a Ni-NTA column. Immunoblotting, ELISA and basophil activation indicated by CD63 expression all confirmed the IgE reactivity and biological activity of rAra h 2. To determine whether or not this allergen plays a role in IgE cross-reactivity between peanut and tree nuts, inhibition ELISA was performed. Pre-incubation of serum from peanut allergic patients with increasing concentrations of almond or Brazil nut extract inhibited IgE binding to rAra h 2. Purified rAra h 2-specific serum IgE antibodies also bound to proteins present in almond and Brazil nut extracts by immunoblotting. This indicates that the major peanut allergen, Ara h 2, shares common IgE-binding epitopes with almond and Brazil nut allergens, which may contribute to the high incidence of tree nut sensitisation in peanut allergic individuals.

Functional analysis of cross-reactive immunoglobulin E antibodies: peanut-specific immunoglobulin E sensitizes basophils to tree nut allergens.

BACKGROUND: Peanut and tree nuts are a major cause of food-induced anaphylaxis with an appreciable mortality. Co-sensitization to peanuts and tree nuts is a common clinical observation and may be because of peanut-specific serum IgE antibodies that cross-react with tree nut allergens. It is, however, unclear whether these cross-reactive IgE antibodies are involved in effector-cell activation. OBJECTIVE: To determine if cross-reactivity of peanut-specific IgE antibodies with tree nuts can cause effector cell activation using an in vitro basophil activation assay. METHODS: Two peanut allergic subjects with positive specific IgE for peanut and tree nuts (as measured by CAP-FEIA) were studied. Basophil activation to peanut and tree nuts, as indicated by CD63 expression, was assessed by flow cytometry to confirm co-sensitization to peanut and tree nuts. Inhibition ELISA using sera from the subjects was performed to detect peanut-specific IgE antibodies that cross-reacted with tree nut proteins. To determine whether cross-reactive tree nut allergens can induce effector-cell activation, peanut-specific antibodies were affinity purified from the subject sera and used to resensitize non-peanut/tree nut allergic donor basophils stripped of surface IgE. Basophil activation was then measured following stimulation with peanut and tree nut extracts. RESULTS: The two peanut allergic subjects in this study showed positive basophil activation to the peanut and tree nut extracts. Inhibition ELISA demonstrated that pre-incubation of the peanut allergic subject sera with almond, Brazil nut and hazelnut extracts inhibited IgE binding to peanut extract. IgE-stripped basophils from non-peanut/tree nut allergic subjects resensitized with affinity-purified peanut-specific antibodies from the peanut allergic subject sera became activated following stimulation with peanut, almond and Brazil nut extracts, demonstrating biological activity of cross-reactive IgE antibodies. CONCLUSION: Peanut-specific IgE antibodies that cross-react with tree nut allergens can cause effector-cell activation and may contribute to the manifestation of tree nut allergy in peanut allergic subjects.

Characterization of the T-cell epitopes of a major peanut allergen, Ara h 2.

BACKGROUND: The development of safe and effective immunotherapy for peanut allergy has been complicated by the high anaphylactic potential of native peanut extracts. We sought to map the T-cell epitopes of the major peanut allergen, Ara h 2 in order to develop T-cell targeted vaccines. METHODS: A panel of eight peanut-specific CD4+ T-cell lines (TCL) was derived from eight peanut-allergic subjects and proliferative and cytokine responses to stimulation with a set of overlapping 20-mer peptides representing the entire sequence of Ara h 2 determined. Proliferation was assessed in 72 h assays via tritiated thymidine incorporation, while interleukin (IL)-5 and interferon (IFN)-gamma production were assessed via sandwich enzyme-linked immunosorbent assay (ELISA) of cell culture supernatants. RESULTS: Eight of the 17 Ara h 2 peptides were recognized by one or more subjects, with the two peptides showing highest reactivity [Ara h 2 (19-38) and Ara h 2 (73-92)] being recognized by three subjects each. Adjoining peptides Ara h 2 (28-47) and Ara h 2 (100-119) induced proliferative responses in two subjects. Each of these peptides was associated with a Th2-type cytokine response. CONCLUSION: Two highly immunogenic T-cell reactive regions of Ara h 2 have been identified, Ara h 2 (19-47) and Ara h 2 (73-119), providing scope for the development of safe forms of immunotherapy for peanut allergy.

Immunological analysis of allergenic cross-reactivity between peanut and tree nuts.

BACKGROUND: Peanut and tree nut allergy is characterized by a high frequency of life-threatening anaphylactic reactions and typically lifelong persistence. Peanut allergy is more common than tree nut allergy, but many subjects develop hypersensitivity to both peanuts and tree nuts. Whether this is due to the presence of cross-reactive allergens remains unknown. OBJECTIVE: The aim of this study was to investigate the presence of allergenic cross-reactivity between peanut and tree nuts. METHODS: Western blotting and ELISA were performed using sera from subjects with or without peanut and tree nut allergy to assess immunoglobulin E (IgE) reactivity to peanut and tree nut extracts. Inhibition ELISA studies were conducted to assess the presence of allergenic cross-reactivity between peanut and tree nuts. RESULTS: Western blot and ELISA results showed IgE reactivity to peanut, almond, Brazil nut, hazelnut and cashew nut for peanut- and tree nut-allergic subject sera. Raw and roasted peanut and tree nut extracts showed similar IgE reactivities. Inhibition ELISA showed that pre-incubation of sera with almond, Brazil nut or hazelnut extracts resulted in a decrease in IgE binding to peanut extract, indicating allergenic cross-reactivity. Pre-incubation of sera with cashew nut extract did not cause any inhibition. CONCLUSION: These results show that multiple peanut and tree nut sensitivities observed in allergic subjects may be due to cross-reactive B cell epitopes present in different peanut and tree nut allergens. The plant taxonomic classification of peanut and tree nuts does not appear to predict allergenic cross-reactivity.

Lung biopsy in diffuse parenchymal lung disease.

This review sets out to define the role of surgical biopsy in the diagnosis and prognosis of diffuse parenchymal lung disease, the pros and cons of each procedure and the interpretation of the results in the context of clinical and other investigative data. Surgical lung biopsy remains the investigation with the greatest overall diagnostic sensitivity for diffuse parenchymal lung disease. Rates of diagnosis are approximately 90-95%, compared with approximately 70% for both high-resolution computed tomography (HRCT) and transbronchial biopsy. Although open lung biopsy, and more recently videoassisted thoracoscopic surgery, have good safety records, neither technique has been utilised as frequently as might be expected, with wide regional variation for various reasons. More recently, HRCT used in conjunction with clinical and other investigative modalities, has increased the accuracy of diagnosis for some diseases, including the majority of cases of cryptogenic fibrosing alveolitis (HRCT & bronchoalveolar lavage), Langerhans' cell histiocytosis (HRCT), lymphangioleiomyomatosis (HRCT), and silicosis (HRCT). At present, the vasculitides and the idiopathic interstitial pneumonias, other than cryptogenic fibrosing alveolitis, always require a surgical biopsy. As experience with high resolution computed tomography grows, it is possible that other diseases will be able to be diagnosed without surgical biopsy. These newer modalities of investigation do have appreciable limitations and where sufficient doubt exists about diagnosis, surgical lung biopsy must continue to be utilised.

The application of high-resolution CT to diagnosis in diffuse parenchymal lung disease.

High resolution computed tomography (CT) now has a central role in the evaluation of diffuse lung disease. It is of particular use in the formulation of a differential diagnosis. Whilst CT often conveys sufficient information to allow non-invasive diagnosis, it sometimes reveals atypical appearances, contributing to the continuing reclassification of diffuse lung disease and justifying histological evaluation in some patients. Thus, CT as a new technology does not always replace conventional diagnostic methods, but is best integrated with clinical assessment, other non-invasive investigations and surgical lung biopsy: this applies equally to clinical diagnosis and to the definition and reclassification of disease entities. In this article, we explore the optimal diagnostic use of CT. The limitations of CT series in simulating the clinical application of CT in the management of diffuse parenchymal lung disease highlight the need for an integrated approach to diagnosis, including corroborative data drawn from many sources. High-resolution computed tomography, when interpreted in the context of the pre-test probability, obviates invasive investigation in many cases. As descriptions of the CT appearances of individual diffuse lung diseases are refined, ongoing re-evaluation is required to establish which features can be regarded as pathognomonic, for diagnostic purposes, and how CT can be integrated into revised disease definitions so that the most clinically relevant diagnostic criteria are formulated.

Predictors of perioperative morbidity and mortality in lung volume reduction surgery.

BACKGROUND: Selection criteria for lung volume reduction surgery are still being refined. We sought to determine whether preoperative features could be used to predict early morbidity or mortality. METHODS: We reviewed preoperative characteristics of the first 89 patients who underwent lung volume reduction surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of stay and reintubation for respiratory failure were used as markers of morbidity. RESULTS: Findings included PaCO2 of 43 +/- 0.7 mm Hg, PaO2 70 +/- 1.1 mm Hg, percent predicted values for forced expiratory volume in 1 second 29.6% +/- 0.8%, TLCO% predicted 35.2 +/- 1.4%, and 6-minute walk test of 315 +/- 10.6 m (mean +/- SEM). Mean length of stay was 19 +/- 2 days, with 17 (19%) patients reintubated for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no deaths in patients less than 65 years old. Multivariate analysis revealed that length of stay, reintubation and mortality were predicted by age and surgical time (p < 0.05), with no correlation with any other variables tested. Age greater than 70 years was associated with a significant risk of mortality (OR 9.0; p = 0.04). CONCLUSIONS: Age greater than 70 years and anesthetic time greater than 210 minutes predict both perioperative morbidity and mortality.

Stinging insect allergies. Assessing and managing.

BACKGROUND: Mortality secondary to insect sting anaphylaxis, though uncommon in this country, is a genuine risk to patients with venom hypersensitivity. A number of non specific and specific preventive measures are available to minimise this risk. They include proper patient counselling regarding sting avoidance and the use of self injectable adrenaline, as well as venom specific immunotherapy. OBJECTIVE: This article attempts to review the spectrum of insect sting reactions, their appropriate assessment and subsequent management. Anaphylaxis is particularly emphasised with regard to first aid treatment and subsequent prevention. DISCUSSION: The most common causes of insect stings in Australia are bees and wasps. Insect sting reactions cover a spectrum of responses, from normal to anaphylactic. Immunotherapy is indicated in those patients who experience anaphylactic responses. The presence of venom specific IgE must be demonstrated before commencing immunotherapy. Venom sensitive patients should be educated in anaphylaxis first aid with adrenaline self injectable syringes.