Dilini Vethanayagam

Osteoporosis-related kyphosis and impairments in pulmonary function : A systematic review

We conducted a systematic review to examine the relationship between osteoporotic vertebral fractures, kyphosis, and pulmonary function. Findings suggest modest but predictable declines in vital capacity related to the degree of kyphosis. However, there were only four studies, and all had significant methodologic limitations. Further high‐quality research is needed.

Hemorrhage Rates From Brain Arteriovenous Malformation in Patients With Hereditary Hemorrhagic Telangiectasia

Background and Purpose— Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain AVMs (HHT-BAVMs). Methods— We studied the first 153 HHT-BAVM patients with follow-up data enrolled in the Brain Vascular Malformation Consortium HHT Project. We estimated ICH rates after BAVM diagnosis. Results— The majority of patients were women (58%) and white (98%). The mean age at BAVM diagnosis was 31±19 years (range, 0–70), with 61% of cases diagnosed on asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases, 37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events occurred yielding a rate of 1.02% per year (95% confidence interval, 0.42–2.44%). ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured cases had a higher ICH rate (10.07%; 95% confidence interval, 3.25–31.21%) than unruptured cases (0.43%; 95% confidence interval, 0.11–1.73%). Conclusions— Patients with HHT-BAVM who present with hemorrhage are at a higher risk for rehemorrhage compared with patients with BAVM detected presymptomatically.

Fragrance materials in asthma: a pilot study using a surrogate aerosol product

Abstract Objective: Many household products contain fragrances. Little is known about exposure to fragrances on human health, particularly within the airways. This study aimed to evaluate how common household fragrance products (i.e. air fresheners, cleaning products) affect people with asthma, who frequently report sensitivity to these products. Many of these products have volatile organic compounds or semi-volatile organic compounds. This study evaluated nine fragrance materials in an aerosol formulation to assess effects on airway physiology, airway inflammation and symptom perception in normal controls and those with asthma. Methods: The effects of fragrances were evaluated in people without asthma, people with mild asthma and people with moderate asthma in a four-way crossover placebo-controlled study. Subjects were exposed twice to a fragranced aerosol and twice to a placebo aerosol (15 and 30 min each). Subjects completed a questionnaire for 29 symptoms during and up to 3 h after each exposure scenario. Spirometry was performed prior to and 3 h post-exposure; sputum induction was conducted 3 h post-exposure. Results: Nasal symptoms showed the greatest frequency of response in all three subject groups, and moderate asthmatics reported the greatest symptom severity and symptom types. No significant differences were noted in physiology or cellular inflammation. Conclusion: A trend for increased symptoms was noted in moderate asthmatics, suggesting that asthma severity may play a factor in fragrance sensitivity.

Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma.

Chemoattractant receptor‐homologous molecule expressed on Th2 cells (CRTh2) is a receptor for PGD2 and expressed by T cells, eosinophils, basophils, and ILC2 cells. CRTh2 expression by CD4+ T cells identifies the Th2 subset, and these cells have been characterized as allergen‐specific central memory Th2 cells. Recently, activation of the PGD2‐CRTh2 pathway in the lungs was associated with severe asthma.

Perceptions About Self-Management Among People with Severe Asthma

Aim. The purpose of this study was to explore the perceptions about self-management among people who were being followed up in a severe asthma clinic by asthma specialists for confirmed, overall severe asthma. Such insight informs how best to tailor programs for this difficult to treat patient population. Method. In-depth tape-recorded interviews of eight adults with severe asthma were transcribed and analyzed for salient themes using content analysis. Results. To self-manage their illness, over time participants sought asthma information from a variety of sources that they often viewed as inadequate due to lack of scope and or plain language. The most valued sources of asthma information were encountered after referral to an asthma specialist and were health professionals and a pulmonary rehabilitation program. Conclusion. There is a need to examine the content of asthma information sources for their relevance to and influence on the behavior of patients with severe asthma.

Hereditary hemorrhagic telangiectasia: transient ischemic attacks

A 39-year-old right-handed man presented to his family physician with sudden-onset weakness in his right arm and leg that had lasted 10 minutes and resolved completely. In the year before presentation, he had an episode of weakness on the right side of his face and difficulty comprehending that had

Increased Protease-Activated Receptor-2 (PAR-2) Expression on CD14++CD16+ Peripheral Blood Monocytes of Patients with Severe Asthma.

Background Protease-Activated Receptor-2 (PAR-2), a G protein coupled receptor activated by serine proteases, is widely expressed in humans and is involved in inflammation. PAR-2 activation in the airways plays an important role in the development of allergic airway inflammation. PAR-2 expression is known to be upregulated in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells in patients with asthma has not been studied. Methods We recruited 12 severe and 24 mild/moderate asthmatics from the University of Alberta Hospital Asthma Clinics and collected baseline demographic information, medication use and parameters of asthma severity. PAR-2 expression on blood inflammatory cells was analyzed by flow cytometry. Results Subjects with severe asthma had higher PAR-2 expression on CD14++CD16+ monocytes (intermediate monocytes) and also higher percentage of CD14++CD16+PAR-2+ monocytes (intermediate monocytes expressing PAR-2) in blood compared to subjects with mild/moderate asthma. Receiver operating characteristics (ROC) curve analysis showed that the percent of CD14++CD16+PAR-2+ in peripheral blood was able to discriminate between patients with severe and those with mild/moderate asthma with high sensitivity and specificity. In addition, among the whole populations, subjects with a history of asthma exacerbations over the last year had higher percent of CD14++CD16+ PAR-2+ cells in peripheral blood compared to subjects without exacerbations. Conclusions PAR-2 expression is increased on CD14++CD16+ monocytes in the peripheral blood of subjects with severe asthma and may be a biomarker of asthma severity. Our data suggest that PAR-2 -mediated activation of CD14++CD16+ monocytes may play a role in the pathogenesis of severe asthma.

Aspergillosis spores and medical marijuana

Thank you for your perspective on medical marijuana as a safer option to narcotics for immunocompromised patients.[1][1] As respirologists, we would like to bring to the attention of all health care workers and administrators the other effects of inhaled marijuana on the respiratory system, whether

Persistent elevation of peripheral blood myeloid cell counts associated with omalizumab therapy.

PURPOSE A case of persistent hematologic abnormalities in a patient receiving long-term omalizumab therapy for severe asthma is reported. SUMMARY During the course of her treatment at an asthma clinic, a 24-year-old woman was noted to have increased white blood cell counts, with elevated myeloid cell counts; the blood abnormalities were first documented more than 12 months previously. The woman had been taking omalizumab for more than 2 years and was also receiving immune globulin therapy for common variable immunodeficiency. Based on the results of bone marrow aspiration and biopsy, she was diagnosed as having mild neutrophilia, possibly related to past corticosteroid therapy, but there was no evidence of a malignancy, a hemophagocytic syndrome, or an infectious, myeloproliferative, or lymphoproliferative process. Pursuant to a multidisciplinary medication review, the use of omalizumab was identified as a potential factor in the myeloid cell elevations and discontinued. About 1 month after omalizumab therapy was halted, the patients myeloid cell counts normalized. The temporal association of omalizumab use and blood abnormalities in this case, coupled with the lack of data on the drugs long-term hematologic effects, suggests a need for cautious use and close monitoring of omalizumab therapy, particularly in younger patients. CONCLUSION A patient with asthma and common variable immunodeficiency developed an elevation of peripheral blood myeloid cells that was first noticed 29 months after the initiation of monthly omalizumab injections. Omalizumab was discontinued, and the abnormality persisted for 1 month after the last dose. The patients blood count results remained within normal limits 3 months after the last dose.

Proteinase-activated receptor-2 (PAR-2) expression on inflammatory cells in severe asthma

Background PAR-2, a G-coupled receptor activated by serine proteinases, is widely expressed in the human body and is involved in inflammation. We have shown that PAR-2 activation in the airways plays a pathogenetic role in mouse models of asthma. PAR-2 expression is increased in the epithelium of asthmatic subjects, but its expression on immune and inflammatory cells of asthmatic individuals has not been. Severe asthma has different phenotypic characteristics from mild-moderate disease. In this study we compared PAR-2 expression on immune cells between subjects with mild/moderate and severe asthma. Methods A total of 36 asthma subjects (24 mild/moderate; 12 severe by ATS guidelines) were recruited at the University of Alberta Hospital and peripheral blood obtained. PAR-2 expression was analyzed by flow cytometry and qRT-PCR in whole blood. Results There were no differences in the % of eosinophils, neutrophils or CD4+ T cells expressing PAR-2 between severe and mild/moderate asthmatics. CD14 high monocytes were classified as classical (CD14++CD16-) or intermediate (CD14++CD16+). No difference in total numbers of either monocyte sub-population was noted between the two asthma groups. More intermediate monocytes from patients with severe asthma (33.6 ±5.1%) expressed PAR-2 compared to patients with mild/moderate asthma (22.4±4.0%, p=0.039), but there was no difference between asthma phenotypes in the percent of classical monocytes expressing PAR-2 (11.7±2.8% vs. 12.5±2.9%). PAR-2 mRNA expression was not different between severe and mild/moderate asthmatics, however, PAR-2 mRNA correlated with total dose of inhaled steroids and inversely correlated with % predicted FEV1. Conclusions PAR-2 expression is increased on intermediate monocytes in subjects with severe asthma. Intermediate monocytes are pro-inflammatory and their numbers are increased in inflammatory diseases. Our data suggest that PAR-2-mediated activation of intermediate monocytes may play ar ole in the pathogenesis of severe asthma, although the effects of PAR-2-mediated activation of these cells are not known.