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Additional file 2: Survey.

Dana Unninayar,1 Sara J Abdallah,2 D William Cameron,2– 4 Juthaporn Cowan2– 4 1Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 2Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 3Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 4Centre of Infection, Immunity and Inflammation, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, CanadaCorrespondence: Juthaporn CowanThe Ottawa Hospital, General Campus, 501 Smyth Road, Box 223, Ottawa, Ontario, K1H 8L6, CanadaTel +1 613-737-8899 X 79617Fax +1 613-737-8352Email jcowan@toh.caAbstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and episodes of worsening respiratory symptoms and pulmonary function, termed acute exacerbations of COPD (AECOPD). AECOPD episodes are associated with heightened airway inflammation and are often triggered by infection. A subset of COPD patients develops frequent exacerbations despite maximal existing standard medical therapy. It is therefore clear that a targeted and more effective prevention strategy is needed. Immunoglobulins are glycoprotein molecules that are secreted by B lymphocytes and plasma cells and play a critical role in the adaptive immune response against many pathogens. Altered serum immunoglobulin levels have been observed in patients with immunodeficiencies and inflammatory diseases. Serum immunoglobulin has also been identified as potential biomarkers of AECOPD frequency. Since plasma-derived polyvalent immunoglobulin treatment is effective in preventing recurrent infections in immunodeficient patients and in suppressing inflammation in many inflammatory diseases, it may be conceivable that immunoglobulin treatment may be effective in preventing recurrent AECOPD. In this article, we provide a review of the current knowledge on immunoglobulin treatment in patients with COPD and discuss plausible mechanisms as to how immunoglobulin treatment may work to reduce AECOPD frequency.Keywords: chronic obstructive pulmonary disease, immunoglobulin treatment, exacerbation

The current study investigated the role of hydrogen sulphide (H2S) in oxygen sensing, intracellular signalling and promotion of ventilatory responses to hypoxia in adult and larval zebrafish (Danio rerio). Both larval and adult zebrafish exhibited a dose-dependent increase in ventilation to sodium sulphide (Na2S), an H2S donor. In vertebrates, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are enzymes that catalyse the endogenous production of H2S. In adult zebrafish, inhibition of both CBS and CSE with aminooxyacetate (AOA) and propargyl glycine (PPG) blunted or abolished the hypoxic hyperventilation, and the addition of Na2S to the water partially rescued the effects of inhibiting endogenous H2S production. In zebrafish larvae (4 days post-fertilization), gene knockdown of either CBS or CSE using morpholinos attenuated the hypoxic ventilatory response. Furthermore, the intracellular calcium concentration of isolated neuroepithelial cells (NECs), which are putative oxygen chemoreceptors, increased significantly when these cells were exposed to 50 μm Na2S, supporting a role for H2S in Ca(2+)-evoked neurotransmitter release in these cells. Finally, immunohistochemical labelling showed that NECs dissociated from adult gill contained CBS and CSE, whereas cutaneous NECs in larval zebrafish expressed only CSE. Taken together, these data show that H2S can be produced in the putative oxygen-sensing cells of zebrafish, the NECs, in which it appears to play a pivotal role in promoting the hypoxic ventilatory response.

Context: Explanations provided by health professionals may underpin helpful or harmful symptom beliefs and expectations of people living with chronic breathlessness. Objectives: This study sought perspectives from health professionals with clinical/research expertise in chronic breathlessness on priority issues in chronic breathlessness explanations and research. Methods: Authors (n = 74) of publications specific to chronic breathlessness were invited to a three-round Delphi survey. Responses to open-ended questions (Round 1 "What is important to: include/avoid when explaining chronic breathlessness; prioritize in research?") were transformed to Likert scale (1-9) items for rating in subsequent rounds. A priori consensus was defined as ≥70% of respondents rating an item as important (Likert rating 7-9) and interquartile range ≤2. Results: Of the 31 Round 1 respondents (nine countries, five professional disciplines), 24 (77%) completed Rounds 2 and 3. Sixty-three items met consensus (include n = 28; avoid n = 9; research n = 26). Explanations of chronic breathlessness should use patient-centered communication; acknowledge the distress, variability, and importance of this sensation; emphasize current management principles; clarify maladaptive beliefs and expectations; and avoid moral culpability and inappropriate reassurance. Research priorities included the need 1) for a comprehensive understanding of breathlessness science; 2) to optimize, explore, and develop effective interventions, both pharmacological and nonpharmacological; and 3) determine effective models of care including strategies for education and training of health professionals and people caring for, or living with, chronic breathlessness. Conclusion: These consensus-based concepts for chronic breathlessness explanations and research provide a starting point for conversations between patients, carers, clinicians, and researchers within the chronic breathlessness community usc Refereed/Peer-reviewed