16 18 2020 april - Canadian Thoracic Society
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Abstracts
Faire avancer le savoir. Advancing knowledge.
CA NADIA N R E SP IRImproving
Améliorer les résultats.
ATOoutcomes.
RY CO N F E R E N C E
april
16
18
april
2020
CTS-SCT.CA/CRC
SHERATON ON THE FALLS, NIAGARA FALLS, ON
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This program has received an educational grant or in-kind support from the following organizations:
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Pharmaceuticals • Novus Medical Inc. • OxyNov • Pentax Medica • Pulmonary Hypertension Association of Canada •
Recruiting Sleep Specialists • RESPTREC® / Lung Association, Saskatchewan • Sanofi Pasteur • Taylor and Francis Group •
THORASYS • Thoracic Medical Systems Inc.
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American Thoracic Society • Canadian Lung Association • CHEST (American College of Chest Physicians) •
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CTS also gratefully acknowledges the support of Health Canada
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CONTENTS
Breakthroughs in Respiratory Diagnostics PG. #
1 The Relationship Between Pulmonary Function and Exhaled Nitric Oxide Levels in Patients with Asthma Ingrid Campbell 1
2 Can Fractional Exhaled Nitric Oxide be Useful to Differentiate Asthma-Chronic Seyed-Mohammad-Yousof Mostafavi-Pour-Manshadi 1
Obstructive Pulmonary Disease (COPD) Overlap (ACO) from COPD-only
3 Diagnostic Accuracy and Reliability of Spirometry with Bronchodilator Testing and Serial Methacholine Challenge Janannii Selvanathan 1
Testing for Diagnosis of Adult Asthma
4 The Diagnostic Accuracy and Reliability of Transcutaneous Carbon Dioxide Monitoring at Home for Nocturnal Jenny Shi 2
Hypoventilation Screening in Children with Neuromuscular Disease
5 Heterogeneity and Altered Lung Mechanics in Lung Allograft Dysfunction using Ventilation SPECT/CT and Anas Tahir 2
Oscillometry Post-Lung Transplant
6 CTPA Scans in Low and Intermediate Probability Patients: Are We Choosing Wisely? Ingrid Wirth 2
7 Establishing In Vitro Equivalence of Legacy and Replacement Wright-Type Nebulizers for Methacholine Challenge Testing Eric Y.L. Wong 3
Challenges in Critical and Clinical Care PG. #
8 Bilateral Pulmonary Emboli Presenting as Intractable Hiccups: A Case Report Brandon Budhram 3
9 Immunity to Influenza A Virus Infection During Pregnancy Julia Chronopoulos 3
10 Prevalence of Cigarette Smoking Amongst Adult Emergency Department Patients Rebecca Erker 4
11 Emergency Department-Based Asthma Prevention: Are We Identifying the Right Patients, and Is this Enough? Tahereh Haji 4
12 A Failure of Occam’s Razor: A Case of Tracheobronchopathia Osteochondroplastica Jennie Parker 4
What's New in COPD? PG. #
13 Systemic Inflammation Is Key to Understanding the Link Between Concomitant Chronic Obstructive Pulmonary Mira Abou Rjeili 5
Disease and Cardiovascular Disease
14 Which Balance Subcomponents Distinguish Between Fallers and Non-Fallers in People with COPD? Stephanie Chauvin 5
15 Contributions of Dual-Task Balance and Gait Performance in People with COPD Cassandra D'Amore 5
16 A High Exacerbation Risk Profile Increases Comorbid Cardiovascular Disease Risk in the Earlier Stages of COPD Particularly Suurya Krishnan 6
When Combined with Worsening Airflow Obstruction: The CanCOLD Study
17 A Review of the Psychometric Properties of Generic Preference-Based Measures in Chronic Obstructive Pulmonary Disease Ava Mehdipour 6
18 A Novel Computer Adaptive Test of Life Participation in People with COPD: Reliability and Validity Sachi O'Hoski 6
19 Pulmonary Capillary Blood Volume is Augmented but Does Not Normalize with Supine Exercise in Patients with Bryan Ross 7
Mild Chronic Obstructive Pulmonary Disease
20 The Relationship Between Self-Efficacy and Functional Exercise Capacity and Physical Activity in People with COPD: Anne-Marie Selzler 7
A Systematic Review and Meta-Analyses
21 Determinants of Sedentary Behaviour in Individuals with COPD: A Qualitative Exploration Guided by Adnan Wshah 7
the Theoretical Domains Framework
2 0 2 0 C A N A D I A N R E S P I R AT O R Y C O N F E R E N C E
Fundamental Research in Respiration PG. #
22 Serum Matrix Metalloproteinase-2 (MMP-2) As A Predictor of Hypoxemic Insult in Obstructive Sleep Apnea Aleksandra Franczak 8
23 The Role of Innate Lymphoid Cells (Ilcs) In A Murine Model of Irritant-Induced Asthma Utako Fujii 8
24 Effect of Anti-Topoisomerase I Antibody Status on Decline in Lung Function in Patients with Systemic Sclerosis-Associated Kristopher Garlick 8
Interstitial Lung Disease: Data from the Senscis Trial
25 Chlorine-Induced Airway Injury Is Mitigated in Mice Treated with A Prostaglandin E2 Receptor 3 Antagonist Emily Nakada 9
26 Characterizing Airway Smooth Muscle-Mediated CD4+ T Cells Recruitment Rui Sun 9
27 A Preclinical Model of Dysanapsis: Fgf10-Haplosufficient Mice Exhibit Airway-to-Lung Size Mismatch and Motahareh Vameghestahbanati 9
A Chronic Obstructive Lung Disease-Like Phenotype
28 Airway Tree Structure Modifies Cigarette Smoke-Associated Lung Function Decline Motahareh Vameghestahbanati 10
29 Airway Tree Structure Modifies Systemic Markers of Cigarette Smoke Uptake Motahareh Vameghestahbanati 10
KT, Community Involvement and Health Care System Approaches: Asthma & CF PG. #
30 Development of an Electronic Medical Record Algorithm for Severe Asthma Emma Bullock 11
31 Improving Pediatric Cystic Fibrosis Post-Clinic Conference Efficiency Kirsten Ebbert 11
32 What Are the Barriers and Enablers to Using A Patient-Facing Electronic Questionnaire for Patients with Asthma? Samir Gupta 11
33 Leveraging An ‘EPIC’ Electronic Medical Record to Reduce Acute Asthma Visits in Children Andrea Higginson 12
34 Development and Validation of a Pragmatic Formula to Convert Between ACT and ACQ-7 Scores in Patients with Asthma M. Hashim Khan 12
35 Asthma Quality Standards: Guiding Evidence-Based, High-Quality Care in the Community for Children, Adolescents, Dhenuka Radhakrishnan 12
and Adults with Asthma in Ontario
KT, Community Involvement and Health Care System Approaches: COPD, ILD & Lung Cancer PG. #
36 Impact of the Interstitial Lung Disease Interdisciplinary Clinic at a Single Center David Fox 13
37 Improving Primary Care Access to Respirologists Using eConsult Jean-Grégoire Leduc 13
38 A Mixed Methods Evaluation of the Implementation of a COPD Management Program Shannon Sibbald 13
39 Health Resource Utilization and Secondary Patient Benefits Achieved Through Continuous Quality Improvement Christopher Stone 14
of a Multidisciplinary Lung Cancer Clinic
40 Involving Patients and Professionals in the Development of a Conceptual Framework for Functional Health Noah Tregobov 14
Literacy to Improve Chronic Lung Disease Outcomes
41 A Risk Perception Model to Promote Smoking Cessation Among Adult Current Smokers: Application of a Noah Tregobov 14
Community-based Smoking Cessation Intervention
2 0 2 0 C A N A D I A N R E S P I R AT O R Y C O N F E R E N C E
Novel Rehabilitation Interventions, Delivery and Outcomes PG. #
42 Outcomes of a Province-Wide Tele-Pulmonary Rehabilitation Program for COPD Patients – a Pilot Study Amr J. Alwakeel1 15
43 Assess, Redress, Re-assess: Addressing Disparities in Sleep Health among First Nations People Mark Fenton 15
44 Collaborative Care and Rapid Access Rehabilitation Roger Goldstein 16
45 Canadian Consensus Recommendations for a Research Agenda in Pulmonary Rehabilitation Post-Acute Exacerbation Tania Janaudis-Ferreira 16
of COPD: A Meeting Report
46 Exertional Oxygen Supplementation Improves Locomotor Muscle Fatigue in Patients with Fibrotic Interstitial Lung Disease Mathieu Marillier 16
47 Priorities in Pulmonary Rehabilitation Research: The Patient Perspective Sachi O'Hoski 17
48 Patient-oriented Outcomes in Pulmonary Rehabilitation of Patients with Interstitial Lung Diseases: A Systematic Review Ana Oliveira 17
49 Augmentation Therapy in Lung Disease due to Alpha-1 Antitrypsin Deficiency: Survival Advantage of Augmented Robert Sandhaus 17
Patients Compared to Matched Augmentation Naïve Patients Followed for up to 15 Years
50 A Pilot Implementation Study of the Canadian Pulmonary Rehabilitation Program Kim van der Braak 18
Palliative Care and Long-term Home Respiratory Management PG. #
51 Comparison of End-of-Life Care in People with COPD or Lung Cancer: A Systematic Review Stacey J Butler 18
52 Paediatric Tracheostomy Care: An Evaluation of an Innovative Competency-Based Education Program for Home Care Nurses Jenny Shi 18
53 A Comparison of Long-Term Non-Invasive Ventilation Use in Down Syndrome and Non-Down Syndrome Children: Rafiaa Valji 19
A Retrospective Regional Cohort Study
54 Tracking Opioid Use as Part of an Early Integrated Palliative Care Approach in Interstitial Lung Disease Laura van den Bosch 19
Pharmacological Fundamentals in Respiration PG. #
55 Efficacy and Safety of Nintedanib In Patients with Systemic Sclerosis-Associated Interstitial Lung Disease by Alison Dungey 20
Use of Mycophenolate at Baseline: Subgroup Analysis of the Senscis Trial
56 Efficacy of Dupilumab in Patients with Type 2 Inflammatory Asthma Enrolled in the Liberty Asthma QUEST Study Mark FitzGerald 20
57 Dupilumab Improves Upper and Lower Airway Outcomes in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) with Leda P. Mannent 21
Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease (NSAID-ERD): Pooled Results From SINUS-24,
SINUS-52 Phase 3 Trials
58 Dupilumab Improves Patient-Reported Outcomes in Chronic Rhinosinusitis with Nasal Polyps With and Without Leda P. Mannent 21
Comorbid Asthma: SINUS-24/SINUS-52 Trials
59 Mechanism of Action of Azithromycin for Prevention of COPD Exacerbations Nafiseh Naderi 21
2 0 2 0 C A N A D I A N R E S P I R AT O R Y C O N F E R E N C E
Breakthroughs in Respiratory Diagnostics
1 subjects with ACO had FENO50 < 25 than those with COPD-only, which was statistically
significant with ACO definition 1 and 3 (p=0.006, 0.024, respectively). The best cut-off
THE RELATIONSHIP BETWEEN PULMONARY FUNCTION AND EXHALED NITRIC values to differentiate ACO from COPD-only were as follows: 18.5 (definition 1), 20
OXIDE LEVELS IN PATIENTS WITH ASTHMA (definition 2), and 17 ppb (definition 3) with sensitivity of 92, 83, 84% and specificity
of 41, 44, 36% for definition 1, 2, and 3, respectively. There was no statistically
Ingrid Campbell1, Larissa Alfonso2, M. Hashim Khan3,4, Kenneth R. Chapman3,4
significant difference between FENO50 for disease severity and progression.
McMaster University, Hamilton, Canada. 2Florida International University, Miami, USA.
1
University Health Network, Toronto, Canada. 4University of Toronto, Toronto, Canada
3 CONCLUSIONS: FENO as a biomarker may have the potential to be used for differentiating
ACO from COPD-only. Further studies should be conducted on a validated definition
ABSTRACT of ACO, which includes a reference to the type of airway inflammation in addition to
RATIONALE: The pathological hallmark of asthma is airway inflammation. Type 2 a clinical definition.
inflammation can be quantified by measuring the fractional concentration of FUNDING: This project was specifically funded by Circassia (formerly Aerocrine). The
exhaled nitric oxide (FeNO). Preliminary data from our centre suggested an Canadian Cohort Obstructive Lung Disease (CanCOLD) study is currently funded by the
association between residual volume (RV) and FeNO level. The present study extended Canadian Respiratory Research Network (CRRN), a consortium of pharmaceutical industry
these pilot data to investigate relationships amongst pulmonary function variables, and previous funding partners are the CIHR (CIHR/ Rx&D Collaborative Research
airway inflammation (as quantified by FeNO) and patient-reported asthma control Program Operating Grants-93326); the Respiratory Health Network of the FRQS.
outcomes.
METHODS: The Asthma & Airway Centre measured asthma patients’ FeNO levels
between March 2016 and July 2019. Data variables obtained were FeNO readings 3
(ppb), RV (L) (% predicted), Asthma Control Test (ACT) scores, Forced Expiratory
DIAGNOSTIC ACCURACY AND RELIABILITY OF SPIROMETRY WITH
Volume in 1 second (FEV1) and bronchodilator responsiveness (BDR) (%).
A retrospective chart review was conducted for patients with a confirmed asthma
BRONCHODILATOR TESTING AND SERIAL METHACHOLINE CHALLENGE
diagnosis who underwent pulmonary function testing and FeNO testing within their TESTING FOR DIAGNOSIS OF ADULT ASTHMA
clinic visit. Regression analysis was conducted to determine significant relationships Janannii Selvanathan1, Shawn Aaron2, Jenna Sykes3, Katherine Vandemheen2,
between lung function variables. Mark FitzGerald4, Martha Ainslie5, Catherine Lemière6, Stephen Field7, Andrew McIvor8,
RESULTS: 211 asthma patients were identified and a significant positive correlation
Paul Hernandez9, Sunita Mulpuru2, Gonzalo Alvarez2, Smita Pakhale2, Ranjeeta Mallick2,
Louis-Philippe Boulet10, Samir Gupta1
between FeNO readings (ppb) and BDR (%) (r=0.167; p=0.018) was observed.
Additional significant positive correlations were seen between BDR (%) and RV (% University of Toronto, Toronto, Canada. 2University of Ottawa, Ottawa, Canada.
1
predicted) (r= 0.358; p
ABSTRACTS | B R E A K T H R O U G H S I N R E S P I R AT O R Y D I A G N O S T I C S
4 chest tissue outside the lung. We found a good correlation of post-LT % drop in FEV1
with CoV (r2 = 0.86 p = 0.01). Correlations were very good with resistance (r2 =0.9,
THE DIAGNOSTIC ACCURACY AND RELIABILITY OF TRANSCUTANEOUS p = 0.001) but lower sensitivity than reactance (r2 = 0.98, p < 0.0001). Correlations
CARBON DIOXIDE MONITORING AT HOME FOR NOCTURNAL HYPOVENTILATION were slightly smaller with VDEF%. The larger change in reactance compared with
SCREENING IN CHILDREN WITH NEUROMUSCULAR DISEASE resistance is indicative of small airway obstruction. There was greater detail in the
pattern of ventilation distribution than captured by our single measures of
Jenny Shi, Jackie Chiang, Munazzah Ambreen, Nadia Snow, Cora Mocanu, Laura McAdam,
ventilation distribution (CoV or VDEF%), which may be useful in early detection of BOS.
Roger Goldstein, Reshma Amin
CONCLUSIONS: Post lung transplant patients showed abnormal lung mechanics of
Division of Respiratory Medicine, The Hospital for Sick Children, Toronto, Canada
the small airways strongly associated with heterogeneity assessed by imaging. Both
ABSTRACT Imaging and oscillometry were more sensitive than spirometry, which may be useful
RATIONALE: Nationally, there is an unmet demand for the evaluation of nocturnal to detect BOS earlier.
hypoventilation in children with neuromuscular disease (NMD). Early screening and
diagnosis is paramount because respiratory failure is the leading cause of morbidity
and mortality in this population. Our aim was to evaluate the diagnostic accuracy of
ambulatory transcutaneous carbon dioxide (tcCO2) monitoring as compared to the
gold standard, laboratory-based polysomnography (PSG), in pediatric patients
with NMD.
METHODS: Prospective, cross-sectional study of pediatric patients 0-18 years old from
the SickKids Long-term Ventilation clinic with confirmed NMD diagnosis that meet
criteria for evaluation of sleep-disordered breathing (SBD) per international
recommendations. Demographics, clinical characteristics, ambulatory tcCO2
(SenTec, Therwil, Switzerland), PSG (with etCO2 and tCO2), and capillary blood gas
data were collected.
RESULTS: 19 NMD patients were recruited but 3 had non-usable ambulatory tcCO2
data due to technical issues: machine failure (1), air bubble (1), and insufficient data 6
time (1). 16 patients aged 13 months to 16 years (mean 10.6 years, SD 5.2 years)
underwent ambulatory tcCO2 monitoring and inpatient PSG for evaluation of nocturnal CTPA SCANS IN LOW AND INTERMEDIATE PROBABILITY PATIENTS: ARE WE
hypoventilation at the time of this report. 14 patients were male; 2 were female. CHOOSING WISELY?
There was no significant difference between the average mean tcCO2 on PSG (mean
Ingrid Wirth, Syed Naqvi, Brent Burbridge, Erika Penz
43.9 mmHg, SD 4.7 mmHg) compared to the ambulatory mean tcCO2 (mean 42.1
mmHg, SD 3.2 mmHg) (p=0.25). Almost all parents, 15/16 preferred it over the PSG. University of Saskatchewan, Saskatoon, Canada
CONCLUSIONS: Ambulatory tcCO2 is a feasible way to screen for nocturnal ABSTRACT
hypoventilation that is well tolerated and preferred by patients and their families. CT pulmonary angiography (also referred to as CTPA) scans are being used with
Mean tcCO2 values were comparable to PSG data, showing that this at-home device increasing frequency to investigate for the presence of pulmonary embolism (PE).
can be a viable way to facilitate more timely and accessible diagnosis and treatment However, their potential risks along with the low rate of positive scans have led to the
of nocturnal ventilation in children with NMD. Additional data with a goal of development of guidelines indicating the most appropriate use of this investigation.
49 participants will be available at the time of the conference. Both Thrombosis Canada and Choosing Wisely Canada recommend that patients
FINANCIAL SUPPORT: Muscular Dystrophy Canada with a low or intermediate pretest probability of PE first undergo d-dimer testing,
and those with a negative d-dimer do not require a CTPA scan. The purpose of this
1 study was to determine whether the use of CTPA scans in Saskatoon hospitals is
5 consistent with the Choosing Wisely and Thrombosis Canada guidelines.
This retrospective review included all CTPA scans performed on non-pregnant adults
HETEROGENEITY AND ALTERED LUNG MECHANICS IN LUNG ALLOGRAFT in Saskatoon hospitals during January, April, July, and October, 2018. 643 scans were
DYSFUNCTION USING VENTILATION SPECT/CT AND OSCILLOMETRY appropriate for inclusion in the study. Pretest probability of PE was determined using
POST-LUNG TRANSPLANT both the Wells and PERC scores.
Anas Tahir1, Chloe Potter1, Alex Brezovan1, Paul Hernandez2,1, Andrew Ross2, 69% of the CTPA scans were performed on patients with a low or intermediate
Meredith Chiasson2, Nancy Morrison2, George Mawko1, Scott Fulton2, Geoff Maksym1 probability Wells score. Only 48% of those patients had a d-dimer tested prior to
Dalhousie, Halifax, Canada. 2QEII Health Sciences Centre, Halifax, Canada
1 the CTPA scan, and 9% of those d-dimers were negative. 1% of the CTPA scans were
performed on patients who had a negative PERC score.
ABSTRACT
Of the scans performed on low or intermediate probability patients with a negative
RATIONALE: Approximately 50% Post lung transplant (LT) patients develop fatal
d-dimer, none were positive for PE. 68% were negative for PE, while the remaining
bronchiolitis obliterans syndrome (BOS) within five years. Decline in FEV1 post LT is
32% were inconclusive. In contrast, 25% of the CTPA scans performed on PERC-negative
our primary measure for determining BOS; however, spirometry is known to be
patients were positive for PE, and the remaining 75% were negative.
insensitive to small airway obstruction, where BOS develops.
The findings that fewer than half of low or intermediate probability patients had
OBJECTIVE: We examined if VSPECT could detect ventilation heterogeneity post LT
a d-dimer tested prior to receiving a CTPA scan, and that approximately 4% of all
and the relationship to spirometry and lung mechanics.
CTPA scans in this study were performed inappropriately on low or intermedi-
METHODS: We measured 8 subjects (age 59.9 ± 8.2, post-LT 6.6 ± 3.4 years, 7/1 M/F). ate probability patients
1
with a known negative d-dimer, demonstrate that greater
Technegas, consisting of Tc-99 embedded carbon particles (Cyclomedica, adherence to the Thrombosis Canada and Choosing Wisely Canada guidelines is
Burlington) was inhaled and imaged supine, with low-dose CT to define chest wall warranted. A quality improvement initiative implementing a clinical decision support
boundary. The coefficient of variation (CoV) and ventilation defect percentage tool may promote more guideline-adherent use of CTPA scans in our health region.
(VDEF%) was calculated from the non-ventilated volume normalized to total lung
volume. These results were compared by Pearson correlation to the drop in FEV1
from best post-transplant value, and also compared to lung mechanics by
oscillometry (TremoFlo, Thorasys, Montreal), which provides the respiratory system
resistance to airflow and low frequency reactance (a measure of lung stiffness).
RESULTS: VSPECT showed heterogeneity even in some subjects with normal lung
function (Fig 1), while with BOS, heterogeneity was more severe with hot spots and
large regions of negligible ventilation (Fig 2). Figures show coronal slices with black
to white indicating particle distribution and ventilation; merged image with CT of
2 0 2 0 C A N A D I A N R E S P I R AT O R Y C O N F E R E N C E 2
ABSTRACTS | B R E A K T H R O U G H S I N R E S P I R AT O R Y D I A G N O S T I C S
7 delivered dose of a 2 mg/mL ciprofloxacin hydrochloride hydrate (CHH) surrogate in
0.9% saline captured on a downstream filter and (ii) residual dry particle sizes from 2
ESTABLISHING IN VITRO EQUIVALENCE OF LEGACY AND REPLACEMENT mg/mL methacholine chloride in 0.9% saline with 0.9% benzyl alcohol. Delivered
WRIGHT-TYPE NEBULIZERS FOR METHACHOLINE CHALLENGE TESTING doses were quantified using UV spectroscopy. Residual particle sizes were measured
using an Electric Low Pressure Impactor. Residual particle mass median aerodynamic
Conor A. Ruzycki1, Tully Underhill1, David Pawluski2, Eric Y.L. Wong2, Warren H. Finlay1,
Andrew R. Martin1 diameters (MMADs) were further interpreted in terms of their content equivalent
diameters, equal to the size of a droplet having the same concentration of
University of Alberta, Edmonton, Canada. 2University of Alberta Hospital, Edmonton, Canada
1
methacholine chloride as the original solution (i.e. 2 mg/mL).
ABSTRACT RESULTS: The delivered dose from the Replacement Wright-Type, 119.1 ± 15.7 µg CHH
RATIONALE: Methacholine challenge testing is commonly used to diagnose airway (average ± standard deviation), showed no significant differences from that of the
hyperreactivity. The Legacy RX160 Wright-Type nebulizer (manufacturer; Roxon Legacy Wright-Type, 125.5 ± 17.6 µg CHH (p = 0.18; student’s t-test). Residual dry
medi-tech, Montreal, QC, Canada), is used in existing protocols for methacholine particle MMADs of the Replacement and Legacy nebulizers also showed no
challenge testing, but is no longer commercially available. A replacement version significant differences (0.64 ± 0.07 versus 0.62 ± 0.06 µm, respectively, corresponding
(Replacement RX160 Wright-Type) with a different manufacturer (A-M Systems, to content equivalent diameters of 2.37 µm and 2.32 µm; p = 0.60).
Sequim, WA, USA) has since been introduced and is commercially available (distributor; CONCLUSIONS: The Legacy and Replacement Wright-Type nebulizers demonstrate
Roxon medi-tech, St-Leonard, QC, Canada). The present study compares the in vitro equivalent delivered doses and particle sizes in vitro. This in vitro equivalency lends
performance of the Legacy and Replacement Wright-Type nebulizers to inform a supports for transitioning to the Replacement Wright-Type nebulizer for
potential transition to the use of the Replacement Wright-Type nebulizer in our methacholine challenge testing.
institution’s pulmonary function laboratory.
INFORMATION ON FINANCIAL SUPPORT: C.A.R. acknowledges scholarship support
METHODS: Five Legacy and five Replacement Wright-Type nebulizers were examined. NSERC, AITF, and The Lung Association AB&NWT. T.U. was supported through a
Nebulizer performance over a 2 minute period was characterized in terms of (i) the NSERC USRA.
Challenges in Critical and Clinical Care
8 9
BILATERAL PULMONARY EMBOLI PRESENTING AS INTRACTABLE HICCUPS: IMMUNITY TO INFLUENZA A VIRUS INFECTION DURING PREGNANCY
A CASE REPORT Julia Chronopoulos1,2,3, Erwan Pernet1,2, Yumiko Ishii1,2, Utako Fujii1,2, James G. Martin1,2,3,
Brandon Budhram, Alisa Lagrotteria, Nischal Ranganath, Conor Cox Maziar Divangahi1,2,3
McMaster University, Division of Internal Medicine, Hamilton, Canada Meakins-Christie Laboratories, Montreal, Canada. 2The Research Institute of McGill University
1
Health Centre, Montreal, Canada. 3McGill University, Montreal, Canada
ABSTRACT
ABSTRACT
INTRODUCTION: Hiccups are the result of involuntary, spasmodic contractions of the
diaphragm and intercostal muscles that are typically transient and innocuous in RATIONALE: Pregnant women are at a higher risk of hospital admissions during
nature. However, investigation is warranted in cases of prolonged hiccups, as this influenza outbreaks. Reproductive hormones during pregnancy modulate the
may be insidious symptomology of an underlying disease. immune system towards a less cytotoxic profile by inducing type 2 immune responses.
Such changes were thought to impair viral clearance; however, studies demonstrate
CASE DESCRIPTION: A previously well 50-year-old male presented to hospital for
that pregnancy induces a robust inflammatory response following influenza A (IAV)
intractable hiccups that were unremitting for five weeks. During this time, multiple
infection. IAV has also been implicated in pulmonary type 2 immunopathology
pharmacological therapies targeted at symptomatic control had been trialed
through the secretion of interleukin (IL-) 33, thymic stromal lymphopoietin (TSLP),
without successful abortion of his hiccups. On day 5 of admission, computed
IL-5, and IL-13 leading to eosinophilia, and airway hyperresponsiveness (AHR).
tomography of the chest demonstrated extensive bilateral pulmonary emboli and
We hypothesize that pregnancy prevents resolution of inflammation following IAV
anticoagulation with rivaroxaban was initiated. His symptoms resolved within 24
infection, resulting in sustained AHR and immunopathology.
hours of anticoagulation, with subsequent down-titration of his symptom-targeted
pharmacotherapy. METHODS: Non-pregnant and pregnant C57Bl/6J mice (gestation day 10/11) were
intranasally infected with PR8, a murine strain of IAV (50 PFU), or with PBS. Airway
DISCUSSION: Herein we describe an unusual case of unprovoked bilateral pulmonary
responsiveness to inhaled methacholine was assessed using FlexiVent and cytokines
emboli presenting as intractable hiccups. A review of the medical literature reveals
known to drive AHR were quantified in the bronchoalveolar lavage (BAL) fluid and
two prior case reports/series of pulmonary embolism presenting as prolonged
lungs by ELISA assays. Key innate immune cells were quantified in the BAL fluid and
hiccups (defined as >48 hours) with a combined sample size of four patients.
whole lung homogenates using flow cytometry. The kinetics of the viral load in the
However, three of these patients had recent surgery and/or malignancy, in
lungs were assessed by MDCK assay, RT-PCR, and flow cytometry to measure
comparison to the patient described in our case report who was devoid of associated
infected epithelial cells positive for IAV nucleoprotein in whole lung homogenates.
risk factors. Although the exact mechanism of pulmonary embolism causing hiccups
Antiviral, pro- and anti-inflammatory cytokines and chemokines were assessed by
is not clear, subsequent diaphragmatic irritation causing activation of the afferent or
ELISA and reporter assay.
efferent limb of the hiccup reflex arc in the chest can been postulated. Following
discharge, the patient has been followed by the Thrombosis team and his symptoms RESULTS: Contrary to our hypothesis, pregnancy conferred protection against
remains in remission. maternal viral infection depicted by a lower pulmonary viral burden, fewer infected
epithelial cells, and less AHR in the mouse. Pregnant mice had lower levels of IL-5,
CONCLUSION: This case report provides further evidence that on rare occasions,
IL-13, TSLP and IL-33 in the airways and fewer ILC2s that produced IL-13 and IL-5.
prolonged hiccups may be the sole presenting symptom of pulmonary embolism.
Moreover, pregnant mice showed less pulmonary eosinophilia at a later time point.
As such, this diagnosis requires consideration in patients presenting with
Pregnant mice exhibited a lower total viral burden, fewer infected epithelial cells,
intractable hiccups.
and more alveolar macrophages, independently of type I and III interferons.
CONCLUSION: The microenvironment of the lung during pregnancy is less conducive
to viral replication thereby controlling the inflammatory response and preserving
native airway function following IAV infection.
3 2 0 2 0 C A N A D I A N R E S P I R AT O R Y C O N F E R E N C E
ABSTRACTS | CHALLENGES IN CRITICAL AND CLINICAL CARE
10 primary care physician. Our secondary outcome was repeat presentation to the ED
within the following year among children who had received RDP versus those who
PREVALENCE OF CIGARETTE SMOKING AMONGST ADULT EMERGENCY had not.
DEPARTMENT PATIENTS RESULTS: 1462 patients were included, and the mean age of those who received RDP
Rebecca Erker, Andrew Tolmie, Emily Sullivan, Thomas Graham, Taofiq Oyedokun, was 5.1 years. In adjusted analysis, children ≥ 6 years were slightly less likely to
James Stempien receive RDP (OR = 0.96 [95% CI: 0.92, 0.99, p=0.04]) and those with a higher PRAM
were most likely to receive RDP (PRAM 4-7: OR = 3.6 [95% CI: 2.5, 5.2], PRAM 8-12: OR
University of Saskatchewan, Saskatoon, Canada
= 3.7 [95% CI: 2.6, 5.3], pABSTRACTS | W H AT ' S N E W I N C O P D ?
What's New in COPD?
13 the BESTest sub-system scores between fallers (participants with ≥1 falls in previous
year) and non-fallers. Receiver operating characteristic (ROC) curves were used to
SYSTEMIC INFLAMMATION IS KEY TO UNDERSTANDING THE LINK determine the subcomponent cut-off scores that had the best sensitivity and
BETWEEN CONCOMITANT CHRONIC OBSTRUCTIVE PULMONARY DISEASE specificity for identifying fallers. The area under the curve (AUC) was used to assess
AND CARDIOVASCULAR DISEASE test accuracy with an AUC ≥ 0.7 considered adequate.
Mira Abou Rjeili1,2, Carolyn Baglole1,2, Jean Bourbeau1,2 RESULTS: Data from 72 subjects with COPD (mean age, 70.3 ± 7.4 y; mean FEV1, 38.9 ±
15.8% predicted) were analyzed. Two of the six BESTest subcomponents, stability
Department of Medicine, Division of Experimental Medicine, McGill University, Montreal,
1
limits/verticality (fallers: 75.4%, non-fallers: 83.8%; p=0.0016) and postural responses
Canada. 2Research Institute of McGill University Health Centre, Montreal, Canada
(fallers: 67.5%, non-fallers: 79.7%; p=0.0084), were able to distinguish between
ABSTRACT fallers and non-fallers. The stability limits/verticality sub-score had an AUC of 0.704
RATIONALE: Chronic obstructive pulmonary disease (COPD) and cardiovascular with a cut-off score of 73.8% for identifying fallers, and postural responses had an
disease (CVD) share similar risk factors, in particular cigarette smoking. Low-grade AUC of 0.669 with a cut-off score of 69.4%.
systemic inflammation is thought to be one of the mechanisms linking COPD and CONCLUSIONS: The stability limits/verticality and postural responses subcomponents
CVD. In response to cigarette smoke, airway epithelial cells (AECs) release the of the BESTest distinguished between fallers and non-fallers with COPD. The stability
pro-inflammatory mediators interleukin (IL)-6 and IL-8 into the systemic circulation. limits/verticality subcomponent can be used to identify whether an
Sustained tissue injury lead to the release of the Damage Associated Molecular individual with COPD is at risk of falling based on a cut-off score of 73.8%. These
Patters (DAMPS) S100A8, S100A9 and IL-1α. This chronic inflammatory state could findings suggest that specific subcomponents of balance, such as how far a person
increase the expression of adhesion molecules including vascular cell adhesion can lean and reach over their base of support, could be targeted to optimize fall risk
protein 1(VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and E-selectin in the assessment and prevention in COPD.
vascular endothelium. This could negatively impact the cardiovascular system by
promoting a pro-thrombotic state. The project is built on the hypothesis that
sustained inflammation secondary to airway epithelial cell (AEC) injury contributes
to the development of CVD in COPD. The objective of this project is to characterize 15
the release of inflammatory biomarkers from AECs and endothelial cells (ECs) in an
in vitro model of cigarette smoke exposure. CONTRIBUTIONS OF DUAL-TASK BALANCE AND GAIT PERFORMANCE IN
METHODS: Normal human bronchial epithelial cells (NHBE) and lung human PEOPLE WITH COPD
microvascular endothelial cells (HMVEC-L) were exposed to 5% cigarette smoke Cassandra D'Amore1, Renata Kirkwood1, Joshua Wald2, Natya Raghavan2,
extract (CSE). Conditioned media from NHBE cells exposed to CSE was collected and Stewart Pugsley2, Marla Beauchamp1,3
added to HMVEC-L cells to compare direct exposure and indirect exposure of ECs to 1
School of Rehabilitation Science, McMaster University, Hamilton, Canada. 2Firestone Institute
CSE. Following exposure, we assessed the expression of inflammatory biomarkers for Respiratory Health, at St Joseph’s Healthcare, Department of Medicine, McMaster University,
IL-6, IL-8,S100A8, S100A9 and IL-1α from AECs and the expression of adhesion Hamilton, Canada. 3Firestone Institute for Respiratory Health, Research Institute at St Joseph’s
molecules VCAM-1, ICAM-1 and E-selectin in ECs by qRT-PCR. Healthcare, Department of Medicine, McMaster University, Hamilton, Canada
RESULTS: Following treatment of NHBE cells with 5% CSE, we observed a significant ABSTRACT
increase in the expression of IL-6, IL-8 IL-1α, S100A8 and S100A9. When HMVEC-L BACKGROUND: Dual task performance-based measures are becoming increasingly
cells were treated with 5% CSE, we observed an increased expression of VCAM-1, popular to measure the interaction between mobility and cognition and to identify
E-selectin but not ICAM-1 expression. When HMVEC-L cells were treated with individuals at increased risk for falls. Individuals with COPD have an elevated risk of
conditioned media, we observed a more significant increase in the expression of falling and understanding the factors that contribute to dual-task gait and balance
VCAM-1, E-selectin and ICAM-1. performance could have implications for fall prevention interventions. The aim of
CONCLUSION: Cigarette smoke promotes inflammation in both epithelial and this study was to determine if measures of functional mobility, cognition and disease
endothelial cells. This suggests that sustained inflammation in patients could be a severity contribute to the prediction of dual task performance in individuals
key mechanism linking COPD and CVD. The funding for this research has been with COPD.
obtained from a CIHR project grant. METHODS: We performed a secondary analysis of baseline data from an ongoing
prospective cohort study on fall risk screening in COPD. Our primary outcome was
the Time Up and Go cognitive dual task test (TUGcog), which consists of timing the
usual standing, walking and turning tasks of the TUG while the participant counts
14 backwards by 3’s. The six-minute walk test (6MWT), 30-second chair-stand test,
single leg stance, FEV1, medical research council dyspnea scale, and the trail making
WHICH BALANCE SUBCOMPONENTS DISTINGUISH BETWEEN FALLERS AND
test part b (TMTb) were investigated as potential predictors. A backwards stepwise
NON-FALLERS IN PEOPLE WITH COPD?
regression analysis with cross validation was performed.
Stephanie Chauvin1, Renata Kirkwood1, Roger Goldstein2,3, Dina Brooks1, RESULTS: Data from 64 individuals with COPD (29 females, mean FEV1 percent
Marla Beauchamp1,4
predicted 45.1, SD 19.9) with a mean age of 72 (SD 6.7) years were included in this
1
Rehabilitation Science, McMaster University, Hamilton, Canada. 2Respiratory Medicine, analysis. Of these, 43% reported one or more falls in the last year. A significant
West Park Healthcare Centre, Toronto, Canada. 3University of Toronto, Toronto, Canada. regression model was found F(3,60)=21.75, pABSTRACTS | W H AT ' S N E W I N C O P D ?
16 17
A HIGH EXACERBATION RISK PROFILE INCREASES COMORBID A REVIEW OF THE PSYCHOMETRIC PROPERTIES OF GENERIC PREFERENCE-
CARDIOVASCULAR DISEASE RISK IN THE EARLIER STAGES OF COPD BASED MEASURES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE
PARTICULARLY WHEN COMBINED WITH WORSENING AIRFLOW Ava Mehdipour1, Marla Beauchamp1,2, Joshua Wald2,1, Nicole Peters1, Ayse Kuspinar1
OBSTRUCTION: THE CANCOLD STUDY
McMaster University, Hamilton, Canada. 2Firestone Institute for Respiratory Health,
1
Suurya Krishnan1,2, Jean Bourbeau1,2, Pei Zhi Li2 Hamilton, Canada
McGill University, Montreal, Canada. 2Research Institute McGill University Health Centre,
1
ABSTRACT
Montreal, Canada
RATIONALE: Generic preference-based measures of health-related quality of life
ABSTRACT (e.g. EQ-5D, HUI3) can aid policymakers, researchers and clinicians to determine
BACKGROUND: The prevalence of cardiovascular disease (CVD) in chronic obstructive which interventions should be implemented that increase good quality life years
pulmonary disease (COPD) increases with severity of airflow limitation. COPD while being cost-effective. However, since these measures are generic and were not
severity is also classified by risk of exacerbations in addition to airflow limitation. developed specifically for people with chronic obstructive pulmonary disease
COPD will increase risk of comorbid CVD as severity of airflow limitation and (COPD), their measurement properties must be evaluated in this population.
exacerbation risk increase. METHODS: A systematic review examining 3 databases: MEDLINE (1946 to July 8th,
METHODS: The Canadian Cohort of Obstructive Lung Disease (CanCOLD) study is a 2019), EMBASE (1974 to July 8th, 2019), and CINAHL (1981 to July 8th, 2019),
longitudinal population-based cohort of mild/moderate plus COPD with age and was performed using Consensus-based Standards for the selection of health
sex matched controls without respiratory disease. Participants were assessed over Measurement Instruments (COSMIN) guidelines. Studies were included if: 1) the
3 years at 3 visits with spirometry, to categorize COPD, and clinical status sample represented individuals with COPD; 2) they included generic preference-
questionnaires that included information on prevalent CVD, defined as self-reported based measures, and 3) the aim was to evaluate one or more psychometric
history of stable/unstable angina, heart failure, coronary artery disease, myocardial properties or the interpretability of generic preference-based measures. Results
infarction, transient ischemic attack or stroke. Exacerbations were assessed every were qualitatively summarized, per property per measure, using mean ranges and
3 months by telephone and high risk was defined as having 2 or more moderate percentage of confirmed hypotheses. In addition, the methodological quality of each
exacerbations (requiring antibiotics/steroids) or one severe exacerbation (requiring study, the rating of each measurement property and the overall quality of evidence
hospitalization) in the previous year. Odds ratios (OR) were calculated for prevalent per measurement property per measure was evaluated. Screening, data extraction
CVD in COPD with varying severities compared to non-COPD adjusting for age, sex, and assessment of methodological quality were all performed by two independent
smoking pack-years and diabetes. reviewers.
RESULTS: Our cross-sectional analysis included all participants that completed the RESULTS: A total of 667 abstracts were screened, resulting in 65 full-text articles for
final CanCOLD visit with information on exacerbations in the previous year; 543 with review and leaving a final 24 articles that met the inclusion criteria. Measures which
COPD GOLD1,2+ and 500 without COPD. Participants with COPD had more comorbid emerged from the search were: the EQ-5D, the SF-6D, the QWB, the 15D and the HUI3,
CVD compared to the non-COPD group, adjusted OR 1.53 (1.00-2.34) for low-risk and with around 70% of studies reporting evidence on the EQ-5D. Studies evaluating
adjusted OR 3.08 (1.48-6.41) for the high-risk group. More disease activity, GOLD 2+ test-retest reliability were low in number and quality. Correlations with generic
further increased the likelihood of prevalent CVD compared to non-COPD, adjusted OR health profiles were moderate to large (0.37-0.68), and correlations with
1.81 (1.01-3.22) for the low-risk and adjusted OR 4.61 (1.90-11.18) for the high-riskgroup. COPD-specific health profiles were large (0.53-0.75). Evidence to support known-
groups validity and responsiveness was weak.
CONCLUSION: The responsiveness of the identified preference-based measures and
their ability to discriminate between different disease severities in COPD was poorly
supported. This suggests a need for the development of COPD-specific preference-
based measures that may allow for a more accurate detection of change and
discrimination amongst different disease severities to facilitate cost-effectiveness
evaluations.
18
A NOVEL COMPUTER ADAPTIVE TEST OF LIFE PARTICIPATION IN PEOPLE WITH
COPD: RELIABILITY AND VALIDITY
Sachi O'Hoski1,2, Julie Richardson1, Joshua Wald3,1, Ayse Kuspinar1, Dina Brooks1,2,4,
Roger Goldstein2,4, Marla Beauchamp1,3,2
McMaster University, Hamilton, Canada. 2West Park Healthcare Centre, Toronto, Canada.
1
CONCLUSION: Compared to those without COPD, the likelihood of comorbid CVD in
St. Joseph's Healthcare, Hamilton, Canada. 4University of Toronto, Toronto, Canada
3
COPD increases by over 200% with a high risk of exacerbations. Combining moderate
plus airflow obstruction with high risk of exacerbations in COPD increased the odds ABSTRACT
of having prevalent CVD by more than 350% compared to the non-COPD group. RATIONALE: Participation in life roles is an often-overlooked part of the assessment
Classification of COPD with severity of airflow obstruction and risk of exacerbations and treatment of people with COPD, perhaps due to the lack of validated measures
can also help identify COPD patients at higher risk of comorbid CVD. of participation in this population. Computer-adaptive versions of static
PROJECT FUNDING: CIHR PJT 152896 Meakins-Christie collaborative research questionnaires are gaining popularity for their ability to increase measurement
studentship precision and decrease administration time. This study aimed to estimate the
test-retest reliability and construct validity of the computer-adaptive version of a
participation measure, the Late Life Disability Instrument (CAT-LLDI), in people
with COPD.
METHOD: Cross-sectional design. Relative (ICC2,1) and absolute (standard error of
measurement [SEM]) and minimal detectable change [MDC90]) reliabilities were
calculated. The relationships between CAT-LLDI scores and scores on the Chronic
Respiratory Disease Questionnaire (CRQ), Hospital Anxiety and Depression scale
(HAD), and Six-Minute Walk Test (6MWT) were examined with correlation coefficients.
Mean CAT-LLDI scores were compared between groups based on symptom severity
(COPD assessment testABSTRACTS | W H AT ' S N E W I N C O P D ?
R E S U L T S : To date, 61 participants (mean age 68.4 (SD 8.0) years; 51% male) have
completed the study (n=14 for test-retest). CAT-LLDI demonstrated moderate to
20
excellent test-retest reliability (ICC2,1 (95%CI) 0.89 (0.65-0.97); SEM (95%CI) 3.15 THE RELATIONSHIP BETWEEN SELF-EFFICACY AND FUNCTIONAL EXERCISE
(2.28-5.08); MDC90 8.73). It had high correlation with the limitation subscale of the CAPACITY AND PHYSICAL ACTIVITY IN PEOPLE WITH COPD: A SYSTEMATIC
static LLDI (r=0.81), moderate correlation with 6MWT (r=0.52), CRQ (r=0.52), REVIEW AND META-ANALYSES
HAD-depression (r=-0.65) and frequency subscale of the static LLDI (r=0.53), and fair
correlation with HAD-anxiety (r=-0.44) (pABSTRACTS | W H AT ' S N E W I N C O P D ?
RESULTS: A total of 867 quotes were mapped to the 14 TDF domains. Seven of the participants, 6% of mapped items) and environmental context and resources (12/14
fourteen domains of the TDF were identified as being important determinants for participants, 4% of mapped items), while the most frequently reported enablers
reducing SB in people with COPD: knowledge, beliefs about consequences, beliefs were related to the domains pertaining to beliefs about consequences (14/14
about capabilities, environmental context and resources, social influences, social/ participants, 10% of mapped items) and social influences (13/14 participants, 9% of
professional role and identity, and behavioural regulation domains. There was a lack mapped items).
of knowledge regarding the meaning of sedentary behaviour (SB). Participants’ CONCLUSION: This study identified the determinants that affect the time spent
desire to be educated by knowledgeable health professionals in a formal program in SB by people with COPD. There is limited understanding of SB concept among
was a dominant theme across multiple domains. The most frequently reported people with COPD. Potential strategies to reduce SB among people with COPD include
barriers related to the domains of social/professional role and identity (14/14 education and other determinants identified in this research.
Fundamental Research in Respiration
22 23
SERUM MATRIX METALLOPROTEINASE-2 (MMP-2) AS A PREDICTOR THE ROLE OF INNATE LYMPHOID CELLS (ILCs) IN A MURINE MODEL OF
OF HYPOXEMIC INSULT IN OBSTRUCTIVE SLEEP APNEA IRRITANT-INDUCED ASTHMA
Aleksandra Franczak1, Jolanta Sawicka2, Andrhea Nocon1, Iwona Bil-Lula3, Mark Fenton1,4, Utako Fujii, Yumiko Ishii, Emily Nakada, Niusha Khazaei, Soroor Farahnak, Toby McGovern,
Grzegorz Sawicki2,3, Robert Skomro1,4 James Martin
Division of Respirology, Critical Care and Sleep Medicine, University of Saskatchewan, Saskatoon,
1
Meakins–Christie Laboratories, McGill University Health Centre Research Institute and the
Canada. 2Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Department of Medicine, McGill University, Montreal, Canada
Saskatoon, Canada. 3Department of Medical Laboratory Diagnostics, Wroclaw Medical
University, Wroclaw, Poland. 4Canadian Sleep and Circadian Network, Saskatoon, Canada ABSTRACT
RATIONALE: Innate lymphoid cells (ILCs) are part of the innate immune system. Type 1
ABSTRACT
ILCs (ILC1s) produce IFN-γ, type 2 ILCs (ILC2s) produce IL-5 and IL-13, and type 3 ILCs
RATIONALE: Upper airway collapse in obstructive sleep apnea (OSA) is associated (ILC3s) produce IL-17. The purpose of the present study was to examine the function
with intermittent hypoxia, which resembles ischemia/reperfusion injury (IRI). IRI has of ILCs in a model of irritant-induced asthma.
been shown to be associated with increased activity of matrix metalloproteinase-2
HYPOTHESIS: ILCs have a protective role in irritant-induced airway dysfunction and
(MMP-2). There is very little and inconsistent information about MMP-2 in OSA. The
inflammation.
objectives of this study were 1) to determine if adult OSA patients have a distinct
serum MMP-2 activity when compared to controls; 2) to determine if serum MMP-2 METHODS: We quantified ILC subtypes (ILC; CD45+ Lineage- CD90+ CD127+, ILC1s;
activity differs in regards to the severity of OSA; 3) to determine if serum MMP-2 T-bet+ ILCs, ILC2s; GATA3+ ILCs, ILC3s; RORγt+ ILCs) in the lung by flow cytometry at 3,
activity differs in regards to the level of hypoxemia. 12, and 24h after chlorine (Cl2) exposure (100 ppm, 5 minutes) in BALB/c mice. We
examined cytokine production by ILCs. We neutralized ILCs by anti-CD90 antibody
METHODS: OSA subjects (n=124) were recruited from the Sleep Disorders Center
(300µg/mouse i.p.) 12h before and 6 h after Cl2 exposure in RAG knockout (RAG-/-)
(Saskatoon City Hospital, Saskatchewan, Canada) after in-lab polysomnography.
mice, deficient T and B cells, and we assessed airway responsiveness to
Controls (n=26) were subjects referred to the Center who did not have OSA. Severity
methacholine by FlexiVent. We administered recombinant IL-33 (100ηg/mouse/day
of OSA was categorized according to American Academy of Sleep Medicine criteria.
intranasally) for 3 successive days to expand ILCs and 1 day after last administration
Oxygen desaturation index (ODI, 3%desaturation) was calculated. Blood samples
we exposed RAG-/- mice to Cl2. We assessed lung function at 24 hours after exposure.
have been collected from all patients in the morning after PSG. Serum was collected,
We neutralized IL-13 with an anti-IL-13 antibody (100μg/mouse i.p.) following
aliquoted and frozen at -80°C until analysis. Gelatin zymography was performed to
IL-33-induced ILC expansion.
measure MMP-2 activity (expressed as arbitrary units/20µl). Mann-Whitney U and
Kruskal-Wallis tests were used for statistical analysis. Results are presented as RESULT: ILCs, ILC2s, and ILC3s increased significantly at 3 and 24h after Cl2 exposure.
median (IQR). IL-5, IL-13, IL-17 production in the ILCs were also increased. Depletion of ILCs did not
affect airway hyperresponsiveness (AHR) and airway inflammation in response to
RESULTS: The cohort was divided into four groups: non-OSA (n=26; AHI 2.8±1.4), mild
Cl2. However, IL-33 administration attenuated AHR and airway neutrophilia. IL-13
(n=43, AHI 9.3±2.9), moderate (n=34, AHI 22.0±4.6) and severe OSA (n=47, AHI
neutralization reversed the effect of IL-33 and restored AHR after Cl2.
63.7±26.1). Serum MMP-2 activity was significantly higher in patients with OSA than
in controls [p = 0.029; 176 (105 – 298) and 135 (93 – 186), respectively]. The highest CONCLUSIONS: The data suggest that IL-33-induced ILCs and the IL-33/IL-13 pathway has
MMP-2 activity was observed in patients with severe OSA. MMP-2 activity in patients a protective role in the development of AHR and airway neutrophilia following Cl2.
with severe OSA [229 (127 – 368)] was significantly higher than in those with FINANCIAL SUPPORT: Supported by a grant from the Canadian Institutes of Health
moderate OSA [133 (90 – 198)] and controls [135 (93 – 186)] (p=0.003). Simple linear Research
regression showed positive associations with MMP-2 activity in serum for AHI
(p=0.001) and ODI (p=0.004). The associations persisted after adjustment for age, sex,
BMI, and CVD. 24
CONCLUSIONS: Serum MMP-2 activity was associated with OSA severity and also with
EFFECT OF ANTI-TOPOISOMERASE I ANTIBODY STATUS ON DECLINE IN
level of hypoxemia in OSA patients.
LUNG FUNCTION IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED
ACKNOWLEDGEMENT: Funded by Canadian Sleep and Circadian Network (CSCN). INTERSTITIAL LUNG DISEASE: DATA FROM THE SENSCIS TRIAL
Maureen Mayes1, Kristin Highland2, Martina Gahlemann3, Ganesh Raghu4, M Girard5,
Margarida Alves6, Susanne Stowasser6, Kristopher Garlick7, Jörg H.W. Distler8,
Marco Matucci–Cerinic9, Elizabeth Volkmann10, Masataka Kuwana11, Oliver Distler12
1
University of Texas McGovern Medical School, Houston, USA. 2Cleveland Clinic, Cleveland, USA.
3
Boehringer Ingelheim, Basel, Switzerland. 4University of Washington, Seattle, USA. 5Boehringer
Ingelheim, Reims, France. 6Boehringer Ingelheim, Ingelheim, Germany. 7Boehringer Ingelheim,
Burlington, Canada. 8University Hospital Erlangen, Erlangen, Germany. 9University of Florence,
Florence, Italy. 10University of California, David Geffen School of Medicine, Los Angeles, USA.
11
Nippon Medical School, Tokyo, Japan. 12UniverUniversity Hospital Zurichsity Hospital Zurich,
Zurich, Switzerland
2 0 2 0 C A N A D I A N R E S P I R AT O R Y C O N F E R E N C E 8ABSTRACTS | F U N D A M E N TA L R E S E A R C H I N R E S P I R AT I O N
ABSTRACT significantly in bronchoalveolar lavage fluid (BALF) in Cl2-exposed mice compared to
INTRODUCTION: The presence of anti-topoisomerase I antibody (ATA) in patients with air controls at both 6 and 24 hours after Cl2 exposure. Increases in AHR (Flexivent)
systemic sclerosis (SSc) has been associated with a greater risk of developing and PGE2 in BALF and lung homogenates (ELISA) occurred. The effects of exogenous
interstitial lung disease (ILD) and greater lung function decline in patients with early PGE2 and inhibition of EP1 and EP3 were examined by intranasally administering
SSc. In the SENSCIS trial, nintedanib reduced the annual rate of decline in forced vital 0.5µg of exogenous PGE2, or 2.5µg of EP1 (GW848687) or EP3 (L-798106) receptor
capacity (FVC) versus placebo in patients with SSc-ILD. antagonist, respectively, 30 minutes before and 5 hours after a single Cl2 exposure.
Exogenous PGE2 administration had no effect on Cl2-induced airway inflammation,
METHODS: Patients with SSc according to the 2013 ACR/EULAR classification criteria,
but exacerbated Cl2-induced AHR. Only the EP3 antagonist significantly reduced
with ≥10% fibrosis of the lungs on a HRCT scan and with onset of the first
Cl2-induced AHR (respiratory system resistance parameter only), and attenuated
non-Raynaud symptom 5% predicted were seen QC, Canada
in 23.1% and 30.5% of patients who were ATA positive (OR 0.69 [95% CI 0.43, 1.10]) ABSTRACT
and 16.7% and 25.2% who were ATA negative (OR 0.59 [0.31, 1.14]) (treatment-by-
BACKGROUND: The mass of airway smooth muscle (ASM) is increased in asthma and
subgroup interaction p=0.73. The adverse event profile of nintedanib was consistent
is associated with disease severity. T cells are found within the asthmatic ASM and in
between patients who were ATA positive and negative.
vitro studies have shown that CD4+ T cells contact-dependently induce airways
CONCLUSION: In the SENSCIS trial in patients with SSc-ILD, the rate of FVC decline smooth muscle cell (ASMC) proliferation. In this study, we examined the chemotactic
over 52 weeks in placebo-treated patients was similar between patients who were signaling responsible for CD4+ T cell recruitment to ASMC, as well as the potential
ATA positive and ATA negative. Nintedanib reduced the rate of FVC decline compared selectivity for certain CD4+ T cell population in this process.
with placebo both in patients who were ATA positive and negative, with a
METHODS: The CD4+ T cell recruitment by ASMC was studied in vitro using Transwell™-
numerically greater treatment effect in patients who were ATA negative.
based modified Boyden Chamber assay where wells of the culture plates are
FINANCIAL SUPPORT: This research is supported by Boehringer Ingelheim. separated into upper and lower chambers by porous membranes that permit T cell
transmigration. ASMCs derived from healthy donors were seeded in the lower
Figure. Annual rate of decline in FVC (mL/yr) over 52 weeks in the SENSCIS trial in subgroups by chambers. Three-day anti-CD3/CD28-activated healthy PBMC-derived human CD4+ T
ATA status at baseline.
cells were seeded in the upper chambers. Following 24-hour incubation, CD4+ T cells
migrated into the lower chambers were collected and quantified. The composition of
ATA positive ATA negative the major CD4+ T subsets among migrated cells was characterized by FACS based on
Nintedanib Placebo Nintedanib Placebo
(n=173) (n=177) (n=114) (n=111) their surface phenotypes. Antagonists targeting several potentially involved
0 chemokine signaling axis were used to identify the ASMC-derived CD4+ T cell
Adjusted annual rate of decline
-20 chemoattractant(s).
-40
in FVC (mL/year)
-35.9 RESULTS: The presence of ASMCs in the lower well enhanced CD4+ T cell migration.
-60 The recruitment process showed no selectivity for any CD4+ T cell subset. The
-80 -63.6 surface level of C-X-C motif chemokine receptor 3 (CXCR3) on CD4+ T cells was
-100 reduced upon exposure to ASMCs, which was likely due to activation-induced
-93.5 -93.1
-120 receptor internalization. ASMC-mediated T cell migration was inhibited by CXCR3
-140 antagonists and by antibody neutralization of CXCR3 ligands. CXCR3 expression was
Difference 29.9 Difference 57.2
(95% Cl-19.1, 78.8)
upregulated among all CD4+ T cells throughout the course of activation, yielding a
(95% Cl-3.5, 118.0)
homogenous CXCR3+ population.
Treatment-by-time-by-subgroup interaction p=0.49 CONCLUSION: ASMCs recruit activated CD4+ T cells via CXCR3-dependent signals.
The homogeneity of CXCR3 expression among the T cells may explain the lack of
recruitment selectivity.
FINANCIAL SUPPORT: This work was supported by a grant from the Natural Sciences
25 and Engineering Research Council of Canada and an internal fellowship from
CHLORINE-INDUCED AIRWAY INJURY IS MITIGATED IN MICE TREATED Department of Medicine, McGill University.
WITH A PROSTAGLANDIN E2 RECEPTOR 3 ANTAGONIST
Emily Nakada, Toby McGovern, Utako Fujii, Yumiko Ishii, William Powell, James Martin
27
Meakins-Christie Laboratories, RI-MUHC, Department of Medicine, McGill University,
Montreal, Canada A PRECLINICAL MODEL OF DYSANAPSIS: FGF10-HAPLOSUFFICIENT MICE
ABSTRACT
EXHIBIT AIRWAY-TO-LUNG SIZE MISMATCH AND A CHRONIC OBSTRUCTIVE
LUNG DISEASE-LIKE PHENOTYPE
RATIONALE: Airway exposure to chlorine (Cl2) induces an influx of macrophages and
neutrophils, increased epithelial shedding, and airway hyperresponsiveness (AHR). Motahareh Vameghestahbanati1, Hussein Traboulsi1, Adam Coates2, Eric Hoffman2,
Mice repeatedly exposed to Cl2 adapt and recruit macrophages expressing high levels of Coralynn Sack3, David Eidelman1, Qutayba Hamid4,1, Carolyn Baglole1, Benjamin Smith1,5
prostaglandin (PG)E2. The role of PGE2 in Cl2-induced airway injury has not been McGill University, Montreal, Canada. 2University of Iowa, Iowa City, USA. 3University of Washington,
1
elucidated. PGE2 exerts anti-inflammatory and bronchodilatory effects via EP2 and Seattle, USA. 4University of Sharjah, Sharjah, UAE. 5Columbia University, New York, USA
EP4 receptors whereas EP1 and EP3 are associated with inflammation and cough. We ABSTRACT
hypothesized that PGE2 attenuates Cl2-induced airway injury via EP2 and EP4 signaling.
RATIONALE: Chronic obstructive pulmonary disease (COPD) is usually caused by
METHODS AND RESULTS: BALB/c mice were nose-only exposed to Cl2 (100ppm for 5 inhalation of noxious particulates, but there is considerable heterogeneity in
minutes), or to air. Neutrophil, macrophage, and epithelial cell numbers increased disease susceptibility and progression. The airway tree, forms early in life, is a major
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