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1.  Asthma in the elderly: a study of the role of vitamin D 
Background
Asthma in the elderly is poorly understood and vitamin D deficiency and insufficiency are very common in older individuals. We studied the role of vitamin D in elderly asthmatics.
Methods
Asthmatics subjects, age 65 and older, were followed every 4 weeks for 12 weeks in the late fall and winter. During the study period they took 2,000 I.U. vitamin D3 daily. Serum 25-Hydroxyvitamin D and calcium were measured at baseline and study end.
Results
Twenty nine percent of subjects were deficient and 50% insufficient in serum vitamin D at baseline. Serum vitamin D increased from 24.3±9.2 ng/ml (60.7±23 nmol/L) to 34±7.1 ng/ml (84.9±17.7 nmol/L) at the end of the study (p<0.001), whereas calcium was unchanged. We found no significant association between vitamin D and subjects' demographics. Vitamin D was similar in men and women. There was no association between serum vitamin D and inhaled steroid dose. Vitamin D was significantly lower in subjects with uncontrolled asthma (Asthma Control Test, ACT≤19) compared to the ones with well controlled symptoms (p<0.05). In subjects with uncontrolled asthma at baseline, ACT scores increased significantly at the end of the study (p<0.04), but not at 4 and 8 weeks. Spirometric values remained unchanged throughout the study.
Conclusions
Elderly asthmatics very commonly have vitamin D deficiency or insufficiency. Serum vitamin D levels were lower in subjects with uncontrolled asthma. In these subjects, vitamin D supplementation for 12 weeks led to improved ACT scores. Larger, randomized, placebo controlled studies are required to further evaluate whether vitamin D supplementation may improve asthma symptoms in this population.
Trial registration
ClinicalTrials.gov NCT01730976.
doi:10.1186/1710-1492-10-48
PMCID: PMC4162927  PMID: 25221606
Asthma; Vitamin D; Elderly
2.  Maternal immunization with ovalbumin or Dermatophagoides pteronyssinus has opposing effects on FcγRIIb expression on offspring B cells 
Background
Over the last decade, our group has demonstrated that murine preconception immunization with allergens has a protective effect on allergy development in offspring. The murine model used in the present study allowed us to compare allergy induction by ovalbumin (OVA) and dust mite extract from Dermatophagoides pteronyssinus (Dp).
Findings
Female mice were immunized with OVA or Dp. Pups from immunized and non-immune mothers were immunized at 3 days old (do) with the same antigen used for the maternal immunization. The offspring were analyzed at 20 do. Preconceptional immunization with OVA or Dp did not increase maternal IgE serum levels, although the immunizations induced an increase in allergen-specific IgG1 Ab levels. Offspring serum analyses revealed that maternal immunization with OVA suppressed IgE production only in offspring immunized with OVA. Both preconception immunization protocols inhibited cellular influx into the airways of immunized offspring compared with controls. Similar frequencies of offspring IgM + B cells were found in the OVA- and Dp-immunized groups compared with their respective control groups. Moreover, preconception immunization with OVA enhanced FcγRIIb expression on OVA-immunized offspring B cells. In contrast, decreased FcγRIIb expression was detected on Dp-immunized offspring B cells compared with cells from the offspring of non-immune mothers.
Conclusions
Together, these results show that preconception OVA immunization and Dp immunization can inhibit allergy development but have opposite effects on FcγRIIb expression on offspring B cells.
doi:10.1186/1710-1492-10-47
PMCID: PMC4161843  PMID: 25221605
Allergy; Maternal immunization; Dermatophagoides pteronyssinus; FcγRIIb
3.  Peripheral blood T cells and neutrophils from asthma patients express class-I MHC-restricted T cell-associated molecule 
Background
Class-I MHC-restricted T cell-associated molecule (CRTAM) is a protein expressed by activated natural killer T (NKT) cells, natural killer (NK) cells, CD8 T cells, and certain CD4 T lymphocytes. It is also expressed in Purkinje neurons and epithelial cells. However, no studies have examined the expression of CRTAM in peripheral blood cells during homeostasis or disease. Therefore, we explored whether CRTAM expression is influenced by the presence of allergic asthma.
Methods
We collected whole peripheral blood cells from non-asthmatic control subjects (n = 17) and patients with asthma (n = 17). All patients with asthma tested positive in allergen skin prick tests. We analyzed CRTAM expression in CD4+ and CD8+ T lymphocyte populations. CRTAM expression was also analyzed in CD177+ neutrophils and IL5Rα+ eosinophils.
Findings
The percentage of CD4+CRTAM+ and CD8+CRTAM+T lymphocytes in peripheral blood was higher in allergic asthma patients compared with healthy controls. Furthermore, the percentage of CD177+CRTAM+ neutrophils in peripheral blood was also elevated in patients with allergic asthma. However, the percentage of IL5Rα+CRTAM+ eosinophils in peripheral blood was not significantly different in patients with allergic asthma compared with healthy controls.
Conclusions
CRTAM expression on T cells, eosinophils, and neutrophils may be involved in bronchial inflammation in allergic asthma. Determination of CRTAM expression in peripheral blood may be useful for the diagnosis of bronchial inflammation and/or to identify recently activated immune cells.
doi:10.1186/1710-1492-10-46
PMCID: PMC4163162  PMID: 25221604
CRTAM; CD355; Asthma; CD4 T cell; CD8 T cells; Neutrophils; Eosinophils
4.  A case of anaphylaxis to peppermint 
Background
Anaphylaxis, a form of IgE mediated hypersensitivity, arises when mast cells and possibly basophils are provoked to secrete mediators with potent vasoactive and smooth muscle contractile activities that evoke a systemic response. We report a case of IgE mediated anaphylaxis to peppermint (Mentha piperita) in a male shortly after sucking on a candy.
Case presentation
A 69 year old male developed sudden onset of lip and tongue swelling, throat tightness and shortness of breath within five minutes of sucking on a peppermint candy. He denied lightheadedness, weakness, nausea, vomiting, or urticaria. He took 25 mg of diphenhydramine, but his symptoms progressed to onset of cough, wheeze and difficulty with talking and swallowing. He was rushed to the nearest emergency department, where he was treated with intramuscular epinephrine, antihistamines and steroids. On history, he reported recent onset of mouth itchiness and mild tongue and lip swelling after using Colgate peppermint toothpaste. He denied previous history of asthma, allergic rhinitis, food or drug allergies. His past medical history was remarkable for hypercholesterolemia, gastroesophageal reflux and gout. He was on simvastatin, omeprazole, aspirin, and was carrying a self-injectable epinephrine device. He moved to current residence three years ago and cultivated mint plants in his backyard. He admitted to develop nasal congestion, cough and wheeze when gardening. Physical examination was unremarkable apart from slightly swollen pale inferior turbinates. Skin prick test (SPT) was strongly positive to a slurry of peppermint candy and fresh peppermint leaf, with appropriate controls. Same tests performed on five healthy volunteers yielded negative results. Skin testing to common inhalants including molds and main allergenic foods was positive to dust mites. Strict avoidance of mint containing items was advised. Upon reassessment, he had removed mint plants from his garden which led to resolution of symptoms when gardening.
Conclusion
IgE mediated anaphylaxis to peppermint is rare. This case demonstrates a systemic reaction to a commonly consumed item, incapable of triggering anaphylaxis in the far majority of the population, yet causing a severe episode for our patient.
doi:10.1186/1710-1492-10-6
PMCID: PMC3912937  PMID: 24472564
Anaphylaxis; Peppermint; Menthol; IgE mediated
5.  T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report 
A girl was diagnosed with cystic fibrosis (CF) at birth, with repeatedly positive sweat tests and homozygous F508del mutations of her CF transmembrane conductance regulator (CFTR) gene. From an early age, her lung disease was more severe than her birth cohort peers despite aggressive treatment. At the age of 16 she was listed for lung transplantation, but prior to transplant was not on systemic corticosteroids or other immunosuppressive agents. In response to ex vivo stimulation, her pre-transplant peripheral blood T cells unexpectedly failed to produce detectable levels of IFN-γ, unlike cells from healthy controls or from another girl with CF and lung disease of comparable severity. Furthermore, naïve T cells freshly isolated from her peripheral blood showed a complete block of T cell differentiation into Th1, Th17 and Treg lineages, even in the presence of cytokines known to promote differentiation into the respective lineages. Her serology has been remarkably devoid of evidence of exposure to viruses that have been associated with T cell exhaustion. However, her freshly isolated naïve T cells showed sustained expression of markers of T cell exhaustion, which were further induced upon ex vivo stimulation, pointing to T cell exhaustion as the cause of the failure of naïve T cells to undergo differentiation in response to cytokine stimulation. Although excessive inflammation in CF lung can be both ineffective at clearing certain pathogens as well as destructive to the lung tissue itself, adequate inflammation is a component of an effective overall immune response to microbial pathogens. Our present findings suggest that intrinsic impairment of T cell differentiation may have contributed to the greater severity and more rapid progression of her CF lung disease than of the lung disease of most of her peers.
doi:10.1186/1710-1492-10-2
PMCID: PMC3896844  PMID: 24438707
T cell exhaustion; Cystic fibrosis; Naïve T cells; T cell differentiation
6.  Hypogammaglobulinemia factitia- Munchausen syndrome masquerading as common variable immune deficiency 
Background
We describe the first case of a patient with factitious disorder who closely simulated a primary immune deficiency disorder – Common Variable Immune Deficiency (CVID), by surreptitiously ingesting non-steroidal anti-inflammatory agents.
Case description
He was treated with several expensive and potentially dangerous drugs before the diagnosis was established through collateral information. In retrospect he did not meet the proposed new criteria for CVID. These criteria may prove useful in distinguishing cases of CVID from secondary hypogammaglobulinemia.
Conclusion
It is imperative clinicians recognise patients with factitious disorder at the earliest opportunity to prevent iatrogenic morbidity and mortality.
doi:10.1186/1710-1492-9-36
PMCID: PMC3848570  PMID: 24341706
Factitious disorder; NSAID; CVID; Hypogammaglobulinemia factitia; Munchausen syndrome
7.  A case of the first documented fire ant anaphylaxis in Canada 
The first documented confirmed case of an imported fire ant causing anaphylaxis in Canada is herein reported. In a patient with anaphylaxis to ants a physician in Canada should be aware that an allergic reaction to fire ant is a possibility.
doi:10.1186/1710-1492-9-25
PMCID: PMC3711928  PMID: 23837799
8.  Proposed new mechanism for food and exercise induced anaphylaxis based on case studies 
We present two cases of food and exercise-induced anaphylaxis (FEIA) in patients with a diagnosis of oral allergy syndrome (OAS) to the implicated foods. Patient A had FEIA attributed to fresh coriander and tomato and Patient B to fresh celery. These food allergens have been implicated in OAS and have structural antigenic similarity to that of birch and/or grass. Both patients’ allergies were confirmed by fresh skin prick tests. In both cases, strenuous exercise was antecedent to the systemic anaphylaxis reaction and subsequent ingestion without exercise produced only local symptoms of perioral pruritus. We review the current proposed mechanisms for food and exercise induced anaphylaxis to oral allergens and propose a novel and more biologically plausible mechanism. We hypothesize that the inhibitory effects of exercise on gastric acid secretion decreases the digestion of oral allergens and preserves structural integrity, thereby allowing continued systemic absorption of the allergen whether it be profilins, lipid transfer proteins, or other antigenic determinants.
doi:10.1186/1710-1492-9-11
PMCID: PMC3608993  PMID: 23509907
Food and exercise-induced anaphylaxis; Food allergy; Exercise; Anaphylaxis; Mechanism
10.  Allergic anaphylaxis due to subcutaneously injected heparin 
Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants.
A 43-year-old patient developed severe anaphylaxis symptoms within 5–10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested.
In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides.
doi:10.1186/1710-1492-9-1
PMCID: PMC3565926  PMID: 23305328
Anaphylaxis; Allergy; Basophil activation test; Enoxaparin; Heparin; Hypersensitivity; Immunoglobulin E; Immediate-type
11.  Anti-neutrophil cytoplasmic antibodies in rheumatoid arthritis: two case reports and review of literature 
Background
Anti-neutrophil cytoplasmic antibodies are typically detected in anti-neutrophil cytoplasmic antibody associated vasculitis, but are also present in a number of chronic inflammatory non-vasculitic conditions like rheumatoid arthritis. Rare cases of granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis, a vasculitic disorder frequently associated with the presence of anti-neutrophil cytoplasmic antibodies) in patients with rheumatoid arthritis have been described in literature.
Case presentation
We report two middle-aged female patients with rheumatoid arthritis who developed anti-neutrophil cytoplasmic antibodies and symptoms reminiscent of granulomatosis with polyangiitis. Despite the lack of antibodies specific for proteinase 3 and the absence of a classical histology, we report a probable case of granulomatosis with polyangiitis in the first patient, and consider rheumatoid vasculitis in the second patient.
Conclusion
Taken together with previous reports, these cases highlight that anti-neutrophil cytoplasmic antibodies have to be evaluated very carefully in patients with rheumatoid arthritis. In this context, anti-neutrophil cytoplasmic antibodies detected by indirect immunofluorescence appear to have a low diagnostic value for granulomatosis with polyangiitis. Instead they may have prognostic value for assessing the course of rheumatoid arthritis.
doi:10.1186/1710-1492-8-19
PMCID: PMC3552688  PMID: 23253567
Granulomatosis with polyangiitis; Rheumatoid arthritis; ANCA associated vasculitis; Rheumatoid vasculitis
12.  Macrophage activation syndrome in a patient with pulmonary inflammatory myofibroblastic tumour 
We describe for the first time a case of macrophage activation syndrome (MAS) in a patient with a history of inflammatory myofibroblastic tumour (inflammatory pseudotumour, IPT) of the lung and thoracic spine. The patient was admitted to the intensive care unit with a history of prolonged remitting fever, hepatosplenomegaly, bilaterally enlarged thoracic lymph nodes and an acute severe inflammatory response syndrome (SIRS). Up-regulated cytokine production (e.g. IL-1ß and IL-6), increased levels of ferritin and circulating soluble interleukin-2 receptor (sIL-2R, sCD25) led to the differential diagnosis of MAS. Bone marrow aspiration, the main tool for a definite diagnosis, revealed macrophages phagocytosing haematopoietic cells. Immunosuppressive therapy with corticosteroids and cyclosporine was an effective treatment in this patient.
doi:10.1186/1710-1492-8-6
PMCID: PMC3473307  PMID: 22607519
Macrophage activation syndrome; Haemophagocytosis; Pulmonary plasma cell granuloma

Results 1-12 (12)