Characteristics of sarcoidosis in Maori and Pacific Islanders.

BACKGROUND AND OBJECTIVE: Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. METHODS: A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. RESULTS: The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). CONCLUSION: People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity.

Chronic cough: a respiratory viewpoint.

PURPOSE OF REVIEW: This article reviews the common causes and investigation of chronic cough and explores unexplained cough and its relationship to cough hypersensitivity. RECENT FINDINGS: Cough plays a critical role in airway protection and clearance of secretions. Chronic cough, however, is a debilitating symptom that can significantly interfere with quality of life. Despite their limitations cough guidelines have raised the awareness of chronic cough as an important problem and provided a framework for a logical care pathway. The use of a systematic approach to diagnosis and management in a specialist clinic can result in successful identification as to the cause, with subsequent relief of symptoms. In a proportion of patients no diagnosis is reached or treatment fails. A common finding among these patients is cough reflex hypersensitivity and this is an important feature irrespective of the underlying diagnosis. The majority of patients referred to tertiary cough clinics are females. Women appear to have an intrinsically heightened cough response with augmented cough challenge and a high frequency of ACE-inhibitor cough. SUMMARY: The way in which we review cough has undergone radical change in the last decade. A distinct population of patients with chronic idiopathic cough is emerging in whom cough reflex hypersensitivity is a feature. Extended co-operation between clinicians, scientists and the pharmaceutical industry is required to better understand the pathophysiology of the enhanced cough reflex and the development of more effective antitussive therapies.

OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis infection claims approximately 2 million lives per year, and improved efficacy of the BCG vaccine remains a World Health Organization priority. Successful vaccination against M. tuberculosis requires the induction and maintenance of T cells. Targeting molecules that promote T-cell survival may therefore provide an alternative strategy to classic adjuvants. We show that the interaction between T-cell-expressed OX40 and OX40L on antigen-presenting cells is critical for effective immunity to BCG. However, because OX40L is lost rapidly from antigen-presenting cells following BCG vaccination, maintenance of OX40-expressing vaccine-activated T cells may not be optimal. Delivering an OX40L:Ig fusion protein simultaneously with BCG provided superior immunity to intravenous and aerosol M. tuberculosis challenge even 6 months after vaccination, an effect that depends on natural killer 1.1(+) cells. Attenuated vaccines may therefore lack sufficient innate stimulation to maintain vaccine-specific T cells, which can be replaced by reagents binding inducible T-cell costimulators.

Prevalence of asthma and atopy in sarcoidosis.

BACKGROUND AND OBJECTIVE: We hypothesized that the prevalence of allergic disorders, characterized by the release of type 2 cytokines (IL-4, IL-5, IL-10), would be lower in sarcoidosis in which there is a dominant type 1 immune response (IL-2, interferon-gamma). The objective was to measure the prevalence of atopy and self-reported asthma in patients with sarcoidosis. METHODS: Sarcoidosis patients (n = 136, 72 M, age range 22-75), recruited in the outpatient setting, completed a modified European Community Respiratory Health Survey. 123 of these patients provided blood for allergy testing. RESULTS: For the cohort as a whole the self-reported prevalence of asthma ever (21.5%) and asthma attack in the last 12 months (7.5%), was high as was wheezing (42.1%), breathlessness with wheeze (22.3%) and use of an asthma medication (13.1%). The prevalence of atopy was 34%. These data are not different from the previously reported prevalence of asthma and atopy in New Zealand. CONCLUSIONS: The same prevalence of asthma symptoms and atopy as in the normal population suggests that the immune system is not skewed away from mounting T helper type 2 immune responses in sarcoidosis.

TGF-beta prevents eosinophilic lung disease but impairs pathogen clearance.

Respiratory infections are the third leading cause of death worldwide. Complications arise directly as a consequence of pathogen replication or indirectly due to aberrant or excessive immune responses. In the following report, we evaluate the efficacy, in a murine model, of nasally delivered DNA encoding TGF-beta1 to suppress immunopathology in response to a variety of infectious agents. A single nasal administration suppressed lymphocyte responses to Cryptococcus neoformans, influenza virus and respiratory syncytial virus. The suppression did not depend on the phenotype of the responding T cell, since both Th1 and Th2 responses were affected. During Th2-inducing infection, pulmonary eosinophilic responses were significantly suppressed. In all cases, however, suppressed immunity correlated with increased susceptibility to infection. We conclude that nasal TGF-beta treatment could be used to prevent pulmonary, pathogen-driven eosinophilic disease, although anti-pathogen strategies will need to be administered concordantly.