Cigarette Smoke, Airway Epithelial Cells and Host Defence

In COPD inflammation driven by exposure to tobacco smoke results in impaired innate immunity in the airway and ultimately to lung injury and remodeling. To understand the biological processes involved in host interactions with cigarette derived toxins submerged epithelial cell culture is widely accepted as a model for primary human airway epithelial cell culture research. Primary nasal and bronchial epithelial cells can also be cultured in models. Air liquid interface (ALI) and submerged culture models have their individual merits, and the decision to use either technique should primarily be determined by the research hypothesis. Cigarette smoke has gaseous and particulate matter, the latter constituent primarily represented in cigarette smoke extract (CSE). Although not ideal in order to facilitate our understanding of the responses of epithelial cells to cigarette smoke, CSE still has scientific merit in airway cell biology research. Using this model, it has been possible to demonstrate differences in levels of tight junction disruption after CSE exposure along with varied vulnerability to the toxic effects of CSE in cell cultures derived from COPD and control study groups. Primary nasal epithelial cells (PNECs) have been used as an alternative to bronchial epithelial cells (PBECs). However, at least in subjects with COPD, PNECs cannot consistently substitute for PBECs. Despite having a constitutional pro-inflammatory phenotype, bronchial epithelial cells retrieved from subjects with COPD have a relatively curtailed inflammatory response to CSE exposure when compared to epithelial cells from thei

Cystic Fibrosis from Laboratory to Bedside: The Role of A20 in NF-κB-Mediated Inflammation

Cystic fibrosis (CF) is a lifelong, inflammatory multi-organ disease and the most common lethal, genetic condition in Caucasian populations, with a median survival rate of 41.5 years. Pulmonary disease, characterized by infective exacerbations, bronchiectasis and increasing airway insufficiency is the most serious manifestation of this disease process, currently responsible for over 80% of CF deaths. Chronic dysregulation of the innate immune and host inflammatory response has been proposed as a mechanism central to this genetic condition, primarily driven by the nuclear factor &amp;#954;B (NF-&amp;#954;B) pathway. Chronic activation of this transcription factor complex leads to the production of pro-inflammatory cytokines and mediators such as IL-6, IL-8 and TNF-α. A20 has been described as a central and inducible negative regulator of NF-&amp;#954;B. This intracellular molecule negatively regulates NF-&amp;#954;B-driven pro-inflammatory signalling upon toll-like receptor activation at the level of TRAF6 activation. Silencing of A20 increases cellular levels of p65 and induces a pro-inflammatory state. We have previously shown that A20 expression positively correlates with lung function (FEV&lt;sub&gt;1&lt;/sub&gt;%) in CF. Despite improvement in survival rates in recent years, advancements in available therapies have been incremental. We demonstrate that the experimental use of naturally occurring plant diterpenes such as gibberellin on lipopolysaccharide-stimulated cell lines reduces IL-8 release in an A20-dependent manner. We discuss how the use of a novel bio-informatics gene expression connectivity-mapping technique to identify small molecule compounds that similarly mimic the action of A20 may lead to the development of new therapeutic approaches capable of reducing chronic airway inflammation in CF.</jats:p

Effect of Aspergillus fumigatus and Candida albicans on pro-inflammatory response in cystic fibrosis epithelium

AbstractBackgroundThe identification of filamentous fungi and/or yeasts in the airway secretions of individuals with cystic fibrosis (CF) is becoming increasingly prevalent; yet the importance of these organisms in relation to underlying inflammation is poorly defined.MethodsCystic fibrosis bronchial epithelial cells (CFBE) and human bronchial epithelial cells (HBE) were co-incubated with Candida albicans whole cells or Aspergillus fumigatus conidia for 24h prior to the measurement of pro-inflammatory cytokines IL-6 and IL-8 by ELISA.ResultsTreatment of HBE or CFBE with C. albicans whole cells did not alter cytokine secretion. However treatment of CFBE with A. fumigatus conidia resulted in a 1.45-fold increase in IL-6 and a 1.65-fold increase in IL-8 secretion in comparison to basal levels; in contrast there was far less secretion from HBE cells.ConclusionOur data indicate that A. fumigatus infection modulates a pro-inflammatory response in CF epithelial cells while C. albicans does not

Development and pilot testing of the 2019 Canadian Abortion Provider Survey

BACKGROUND: Substantial changes in abortion care regulations, available medications and national clinical practice guidelines have occurred since a 2012 national Canadian Abortion Provider Survey (CAPS). We developed and piloted the CAPS 2019 survey instrument to explore changes of the abortion provider workforce, their clinical care as well as experiences with stigma and harassment. METHODS: We undertook development and piloting in three phases: (1) development of the preliminary survey sections and questions based on the 2012 survey instrument, (2) content validation and feasibility of including certain content aspects via a modified Delphi Method with panels of clinical and research experts, and (3) pilot testing of the draft survey for face validity and clarity of language; assessing usability of the web-based Research Electronic Data Capture platform including the feasibility of complex skip pattern functionality. We performed content analysis of phase 2 results and used a general inductive approach to identify necessary survey modifications. RESULTS: In phase 1, we generated a survey draft that reflected the changes in Canadian abortion care regulations and guidelines and included questions for clinicians and administrators providing first and second trimester surgical and medical abortion. In phase 2, we held 6 expert panel meetings of 5-8 participants each representing clinicians, administrators and researchers to provide feedback on the initial survey draft. Due to the complexity of certain identified aspects, such as interdisciplinary collaboration and interprovincial care delivery differences, we revised the survey sections through an iterative process of meetings and revisions until we reached consensus on constructs and questions to include versus exclude for not being feasible. In phase 3, we made minor revisions based on pilot testing of the bilingual, web-based survey among additional experts chosen to be widely representative of the study population. Demonstrating its feasibility, we included complex branching and skip pattern logic so each respondent only viewed applicable questions based on their prior responses. CONCLUSIONS: We developed and piloted the CAPS 2019 survey instrument suitable to explore characteristics of a complex multidisciplinary workforce, their care and experience with stigma on a national level, and that can be adapted to other countries

Telemedicine for First-Trimester Medical Abortion in Canada: Results of a 2019 Survey.

Telemedicine has the potential to improve abortion access disparities in Canada. We aimed to explore the provision of telemedicine for first-trimester medical abortion and related barriers in 2019. Methods: We conducted a national, cross-sectional, anonymized, web-based survey of clinicians who provided abortion care in 2019 in Canada. We distributed our survey through professional health organizations to maximize identification of possible eligible respondents and used a modified Dillman technique to foster responses. Questions elicited provider demographics, clinical characteristics, including telemedicine first-trimester medical abortion and perceived related barriers. Descriptive statistics were analyzed using R software. Results: Among 465 respondents, 388 reported providing first-trimester medical abortion across Canada; 44.0% reported experience using telemedicine for some components of care: 49.3% of primary care clinicians and 28.7% of specialists. Telemedicine was used for initial consultation (86.0%), prescription (82.2%), or follow-up (92.2%). The median percentage of telemedicine providers' patients who underwent a dating ultrasound was 90.0. The majority usually followed up with patients through quantitative human chorionic gonadotropin (hCG) (84.2%). Seventy-eight percent perceived barriers to telemedicine; the most common being inability to confirm gestational age with ultrasound (43.0%), and lack of provincial telemedicine abortion fee code to pay practitioners (30.2%), timely access to serum hCG testing (24.6%), and nearby emergency services (23.3%). Discussion: In 2019, fewer than half of respondents reported providing some aspects of first-trimester medical abortion through telemedicine and the majority perceived barriers. Our results can inform knowledge translation activities to reduce barriers and increase telemedicine abortion care in Canada

First and Second Trimester Surgical Abortion Providers and Services in 2019: Results from the Canadian Abortion Provider Survey

OBJECTIVE: Our objective was to explore the workforce and clinical care of first and second trimester surgical abortion (FTSA, STSA) providers following the publication of updated Society of Obstetricians and Gynaecologists of Canada (SOGC) surgical abortion guidelines. METHODS: We conducted a national, cross-sectional, online, self-administered survey of physicians who provided abortion care in 2019. This anonymized survey collected participant demographics, types of abortion services, and characteristics of FTSA and STSA clinical care. Through health care organizations using a modified Dillman technique, we recruited from July to December 2020. Descriptive statistics were generated by R Statistical Software. RESULTS: We present the data of 222 surgical abortion provider respondents, of whom 219 provided FTSA, 109 STSA, and 106 both. Respondents practiced in every Canadian province and territory. Most were obstetrician-gynaecologists (56.8%) and family physicians (36.0%). The majority of FTSA and STSA respondents were located in urban settings, 64.8% and 79.8% respectively, and more than 80% practiced in hospitals. More than 1 in 4 respondents reported <5 years' experience with surgical abortion care and 93.2% followed SOGC guidelines. Noted guideline deviations included that prophylactic antibiotic use was not universal, and more than half of respondents used sharp curettage in addition to suction. Fewer than 5% of STSA respondents used mifepristone for cervical preparation. CONCLUSIONS: The surgical abortion workforce is multidisciplinary and rejuvenating. Education, training, and practice supports, including SOGC guideline implementation, are required to optimize care and to ensure equitable FTSA and STSA access in both rural and urban regions

Nurse practitioner medication abortion providers in Canada: results from a national survey.

BACKGROUND: In 2017, nurse practitioners (NPs) became the first non-physician healthcare providers authorised to independently provide medication abortion (MA) in Canada. We aimed to report on demographic and clinical characteristics of NPs providing mifepristone/misoprostol MA in Canada and to identify context-specific barriers and enablers to NP provision of mifepristone/misoprostol MA in Canada among MA providers and non-providers. METHODS: From August 2020 to February 2021, we invited Canadian NPs to complete a national, web-based, bilingual (English/French) survey. The survey was distributed through national and provincial nursing associations and national abortion health professional organisations. We collected demographic and clinical care characteristics and present descriptive statistics and bivariate analyses to compare the experiences of NP providers and non-providers of MA. RESULTS: The 181 respondents represented all Canadian provinces and territories. Sixty-five NPs (36%) had provided MA at the time of the survey and 116 (64%) had not. Nearly half (47%) of respondents worked in rural or remote communities and 81% in primary care clinics. Significant barriers impacting non-providers' abilities to provide MA included limited proximity to a pharmacy that dispensed mifepristone/misoprostol, few experienced abortion providers in their community of practice, poor access to procedural abortion services, policy restrictions in NPs' places of employment, and no access to clinical mentorship. Some 98% of NPs providing MA services had never encountered anti-choice protest activity. CONCLUSIONS: NPs appear prepared and able to provide MA, yet barriers remain, particularly for NPs in smaller, lower-resourced communities. Our findings inform the development of supports for NPs in this new practice to improve abortion access in Canada

The perspective of Canadian health care professionals on abortion service during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic and pandemic response created novel challenges for abortion services. Canada was uniquely positioned to transition to telemedicine because internationally common restrictions on abortion medication were removed before the pandemic. OBJECTIVE: We sought to characterize the experiences of abortion health care professionals in Canada during the COVID-19 pandemic and the impact of the pandemic response on abortion services. METHODS: We conducted a sequential mixed methods study between July 2020 and January 2021. We invited physicians, nurse practitioners and administrators to participate in a cross-sectional survey containing an open-ended question about the impact of the pandemic response on abortion care. We employed an inductive codebook thematic analysis, which informed the development of a second, primarily quantitative survey. RESULTS: Our initial survey had 307 respondents and our second had 78. Fifty-three percent were family physicians. Our first survey found respondents considered abortion access essential. We identified three key topicss: access to abortion care was often maintained despite pandemic-related challenges (e.g. difficulty obtaining tests, additional costs); change of practice to low-touch medication abortion care and provider perceptions of patient experience, including shifting demand, telemedicine acceptability and increased rural access. The second survey indicated uptake of telemedicine medication abortion among 89% of participants except in Quebec, where regulations meant procedures were nearly exclusively surgical. Restrictions did not delay care according to 76% of participants. CONCLUSIONS: Canadian health care professionals report their facilities deemed abortion an essential service. Provinces and territories, except Quebec, described a robust pandemic transition to telemedicine to ensure access to services. PODCAST: An accompanying podcast is available in the Supplementary Data, in which the authors Dr Madeleine Ennis and Kate Wahl discuss their research on how family planning care and access to abortion services have changed during the COVID-19 pandemic