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. 2012 May-Jun;19(3):e31–e50.

A Breath of Fresh Air / Une boufée d’air frais: Abstracts from the 2012 Canadian Respiratory Conference

April 26 – 28, 2012, Vancouver, British Columbia

Pearce Wilcox 1, Pearce Wilcox 2
PMCID: PMC3418102

Abstract

The present online supplement highlights the poster abstracts selected for presentation at the 5th Annual Canadian Respiratory Conference (CRC) held in Vancouver, British Columbia, in April 2012. The CRC is a partnership initiative of the Canadian Thoracic Society, Canadian Respiratory Health Professionals, The Lung Association and the Canadian COPD Alliance and has become the premiere national educational and scientific meeting for the respiratory community in Canada. I would like to acknowledge the leadership and expertise of the Scientific Committee, our conference speakers and abstract presenters, all of whom contributed to the delivery of an excellent program. The next Canadian Respiratory Conference will be held in Québec City, Quebec, April 11 to 13, 2012 (www.lung.ca/crc). We look forward to seeing you there!

Can Respir J. 2012 May-Jun;19(3):e33.

1: Anti-Apoptotic Effect of 1 25-Dihydroxycholecalciferol on Eosinophils from Allergic Asthmatics

Caroline Éthier 1, Fanny Pallot 1,*, Isabelle Chapados 2, Yingqi Wu 1, Darryl James Adamko 1,4, Francis Davoine 1,*

Abstract

RATIONALE

The prevalence of allergic diseases and asthma has increased worldwide at least during the last 3 decades. Meanwhile the incidence of various autoimmune and allergic conditions appears to be higher further away from equator. Amongst the hypothesis suggested to connect these observations is the lack of exposure to sufficient sunlight and therefore relative vitamin D deficiency. Mucosal dendritic cells can hydroxylate vitamin D into bioactive calcitriol (1.25-dihydroxycholecalciferol). This hormone suppresses Th17 and Th1 cytokine production by Th lymphocytes and therefore contributes to reduction in allergic inflammation. Although, nothing is known about the possible direct activity of calcitriol on eosinophils, an inflammatory cell characteristic of lung mucosal infiltration in allergic asthma.

HYPOTHESIS:

Calcitriol exerts mucosal regulatory effect directly on eosinophils.

METHODS:

Blood eosinophils from atopic asthmatic donors were isolated and incubated with physiological concentrations of calcitriol (0 to 100 nM). Annexin V-PI flow cytometry assay was used to measure apoptosis and viability of eosinophils.

RESULTS:

Preliminary results indicate that increasing concentrations of calcitriol are able to sustain viability of blood eosinophils in vitro without the addition of any other anti-apoptotic factors (n=6, p<0.05). Over a 7-day period, an additive effect of calcitriol on eosinophils viability is observed, when co-cultured with IL-5.

CONCLUSION:

Our preliminary data suggests that calcitriol is a potent immune regulator of eosinophil viability. Reduced eosinophils mortality may be associated with a reduction of mediator shedding in mucosa from necrotic and apoptotic eosinophils. We hope to unveil some other activities of this vitamin on eosinophils and perhaps explain further the complex physiopathology of allergic asthma.

Can Respir J. 2012 May-Jun;19(3):e33.

2: Development of a Tubular Nano-Fiber Scaffold for Functional Study of Human Airway Smooth Muscle Cells

Min Hyung Ryu 1,6,8, Samuel Wadsworth 7,8, Delbert Dorscheid 7,8, Malcolm Xing 4,5,6,8, Gerald L Stelmack 1,6, Helmut Unruh 2, Andrew J Halayko 1,2,3,6,8

Abstract

RATIONALE

Bio-engineered tissues are needed for reliable translation of pre-clinical data. Bioengineered nano-fiber scaffolds exhibit biocompatibility and mimic three dimensional tissue structure. Intrinsic stiffness of engineered scaffolds determines cell fate, survival, and phenotype, thus unique physical properties are needed for specific cell types. Airway smooth muscle (ASM) encircles the bronchi and controls airway caliber, the principal factor that determines airflow resistance. Therefore, optimizing a scaffold matrix to support long-term survival and contractile function of ASM is essential to develop functional, multi-cellular bioengineered human airways for experimentation.

METHODS:

Polyhydroxybutyrate (PHB) and gelatin, 1:1 by weight, were co-electrospun on a high speed rotating metal rod to create circumferentially aligned nano-fibrous tubular scaffolds. Ultrastructure of scaffolds was assessed using scanning electron microscopy (SEM). The passive length-tension (L-T) relationship of scaffolds was assessed by myography; change during prolonged cell-free culture was assessed. Primary human ASM cell adherence to the scaffolds in DMEM/0.5% fetal bovine serum culture medium was assessed by cell counting.

RESULTS:

We electrospun tubular, 2 mm diameter scaffold in which nano-fibres were circumferentially aligned (see figure). The passive L-T relationship of scaffolds was exponential in nature (eg. 0.00023.48x, R2=0.96, 5 days culture). Scaffold elasticity was decreased after 4 weeks in cell-free culture (0.00053.69x, R2=0.98). The PHB:gelatin scaffold supported significant adherence of human ASM cells, attaining a cell density of 3.1×104/cm2 48 hrs after seeding. Notably, 78.8% of these cells adhered within 2 hrs of seeding.

graphic file with name crj19e0311.jpg

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CONCLUSION:

PHB:gelatin is suitable to generate tubular nano-fibrous scaffolds with structural, mechanical and chemical properties that mimic intact airways and support adherence and spreading of human ASM cells. This approach offers potential to develop functional bioengineered airways harboring human cells.

Footnotes

Funding: National Sanitarium Association and MICH. AJH is supported by Canada Research Chairs Program

Can Respir J. 2012 May-Jun;19(3):e33–e34.

3: Investigation of the Barrier Properties of Differentiated Human Airway Epithelium from Normal and Asthmatics In Vitro

C Leung 1, S Wadsworth 1, D Dorscheid 1

Abstract

RATIONALE

The airway epithelium forms a barrier against inhaled noxious substances, simultaneously transporting certain molecules into the airway lumen. In asthma the airway epithelium is held in a repair phenotype which may prevent the development of normal barrier function. We used primary human bronchial epithelial cells (HBECs) from normals and asthmatics to investigate barrier functions in health and disease in vitro.

METHODS:

Primary HBECs from normals and asthmatics were differentiated into a mucociliated phenotype in specialised PneumaCult-ALI (StemCell) media for 21 days in air-liquid interface (ALI) culture. At weekly time-points barrier function was assessed by trans-epithelial electrical resistance (TEER), and permeability by diffusion of FITC-labeled dextran (4kDa) and horseradish peroxidase (HRP, 44kDa). At 21d ALI, cultures were fixed and stained to image culture morphology and junctional protein expression.

RESULTS:

Pneumacult-ALI cultures are stratified and mucociliated. At 14d post-ALI, cells from asthmatic donors demonstrated significantly greater TEER (501.8Ω.cm2±59.4 SD) compared to normal cultures (193.8Ω.cm2 ±59.4 SD, p<0.0001). At all time points normal and asthmatic cells demonstrated approximately 10–fold greater diffusion of 4kDa dextran than 44kDa HRP. At d0 ALI, normal and asthmatic cultures demonstrated similar diffusion rates in apical to basal (A-B), and basal to apical (B-A) directions. At d14 ALI, normal cells developed significantly greater diffusion rates in the B-A direction than A-B for 4kDa dextran and 44kDa HRP. In contrast, cultures from asthmatic donors did not demonstrate higher diffusion rates in the B-A direction for either tracer molecule.

CONCLUSION:

We have demonstrated airway epithelial cultures from asthmatic donors are less permeable than normals as measured by TEER, but they do not develop asymmetrical barrier properties, and in this respect are similar to undifferentiated cultures of normals cells. Our data suggests the “immature” epithelium in asthmatic airways forms an intact barrier, but a lack of basal-apical trans-epithelial molecular transport may compromise innate immune functions, such as immunoglobulin transport.

Footnotes

Funding: The National Sanitarium Association.

Can Respir J. 2012 May-Jun;19(3):e34.

4: Plasma Proteomics of Asthmatic Individuals Undergoing Allergen Inhalation Challenge

Amrit Singh 1,2, Gabriela V Cohen Freue 2,3,4, Jean L Oosthuizen 1,2, Sarah H Y Kam 1,2, Jian Ruan 1,2, Mandeep K Takhar 2,3, Gail M Gauvreau 5, Paul M O’Byrne 5, J Mark FitzGerald 2,6,7, Louis-Philippe Boulet 8, Christoph H Borchers 9, Scott J Tebbutt 1,2,3,6

Abstract

RATIONALE

Atopic asthmatic individuals respond differently, but reproducibly, to allergen inhalation challenge (AIC). Some individuals develop an isolated early response while others develop isolated late or dual responses. The purpose of this study was to identify proteomic bio-signatures of isolated early and dual responses induced through allergen inhalation challenge.

METHODS:

Eight adult subjects [4 early responders (ERs) and 4 dual responders (DRs)] participated in the AIC. Blood samples were collected prior to and 2h after the inhalation challenge. 16 plasma samples (2 per subject) as well as pooled controls were analyzed using isobaric Tags for Relative and Absolute Quantitation (iTRAQ) mass spectrometry. Data was processed using ProteinPilot™ and summarized using the Protein Group Code Algorithm. Moderated robust regression in R (statistical computing program) was used to determine differentially expressed Protein Groups (PGs) using an FDR cut-off of 15%. Ingenuity Pathway Analysis (IPA) was used to determine biological functions, canonical pathways and networks.

RESULTS:

28 (10 over-expressed and 18 under-expressed) PGs were found to be differentially expressed when comparing ER and DRs at pre-challenge. Complement proteins were significantly under-expressed in DRs relative to ERs at pre-challenge. Fibronectin (FN1) was differentially expressed between ERs and DRs at both pre- and post-challenge time points. IPA indicated Infectious Disease, Inflammatory Response, Antigen Presentation, Cell-To-Cell Signaling and Interaction and Hematological System Development as the top biological functions.

CONCLUSIONS:

Proteomic analysis has shown significant differences between ERs and DRs prior to and following AIC. Reduced expression of complement proteins in DRs implicates innate immunity in asthmatic responses. FN1 levels suggest differences in the extent of tissue remodeling between ERs and DRs. Thus, the AIC model may improve understanding of molecular mechanisms associated with asthma.

Footnotes

Financial support: BC Proteomics Network (MSFHR); AllerGen NCE Inc. (Allergy, Genes and Environment Network); Canadian Institutes of Health Research

Can Respir J. 2012 May-Jun;19(3):e34.

5: Environmental Challenge and IL-33 Release by Airway Epithelial Cells

Gurpreet K Singhera 1, Jeremy Hirota 1, Tillie Hackett 1, Darryl Knight 1, Delbert R Dorscheid 1

Abstract

RATIONALE

Interleukin (IL)-33 is a novel member of the IL-1 family with a dual function, as a cytokine acting through activation of the ST2L receptor and as an intracellular nuclear factor with potential transcriptional regulatory properties. As an “alarmin molecule” it induces either pro- or anti-inflammatory cascades. In this study we have investigated the localization of IL-33 in diseased human airways and the specific challenges that affect IL-33 production and release.

AIM:

Characterize IL-33 expression in asthmatic and non-asthmatic airway epithelial cells (AEC) and the specific signals required for IL-33 release.

METHODS:

Using immunohistochemistry (IHC) techniques, IL-33 expression was characterized in airway sections of normal and diseased airways (asthma, COPD and cystic fibrosis (CF) from the JHRC Biobank using semi-quantitative scoring tool. In an in vitro model, primary human bronchial epithelial cells (HBEC) were incubated with RSV, Thrombin, Fas, or TRAIL and subsequent detection of IL-33 by either ELISA or Western Blots (WB).

RESULTS:

IHC data demonstrates that in airway sections from all donors IL-33 is characterized predominantly by a nuclear pattern within the basal cells of the epithelium. With respect to normal tissue, asthmatic airways demonstrate a non-significant increase in IL-33 detection. However asthmatic airways had a significant increase in IL-33 when compared to COPD and CF airways. In vitro AEC experiments demonstrated higher IL-33 release from asthmatic AEC at baseline and after stimulation. Compartmentalization of IL-33 between total cellular and nuclear fractions was altered with similar stimulation.

CONCLUSIONS:

In summary, IL-33 release can be induced from AEC. IL-33 plays a role in allergic processes and interestingly there is less IL-33 detection in COPD/CF airways, diseases thought to be mediated by neutrophils. Understanding the regulation of IL-33 expression as determined by environmental challenges is important to affect better control of allergic inflammation as a contributor in asthma.

Footnotes

Funding: CIHR: Allergen, NCE

Can Respir J. 2012 May-Jun;19(3):e34–e35.

6: Surfactant Protein-A and -D Expression in Airway Epithelium of Asthmatics and its Modulation by Viral Infection

Janet Xu 1, Gurpreet K Singhera 1, Delbert R Dorscheid 1

Abstract

RATIONALE

Surfactant proteins (SP) are part of the innate immune system as pattern recognition molecules. Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections and has been linked to the asthma etiology. SP-A and SP-D have been reported in the clearance of RSV. Characterization of surfactant protein expression may contribute to the understanding of asthmatic susceptibility to viral infection.

AIM:

Characterize SP-A and -D expression in asthmatic and non-asthmatic airway epithelial cells (AEC).

METHODS:

Human airway sections from asthmatic and non-asthmatics and sections of pseudostratified air-liquid interface (ALI) were used to quantify SP-A and SP-D by immunohistochemistry. Protein levels of SP-D were determined using Western blotting on protein lysates of both RSV infected and non-infected human AEC.

RESULTS:

Both SP-A and SP-D molecules were expressed in intact human airway sections. SP-A expression was low and localized mainly in small airways whereas SP-D expression was highly expressed and detected in airways of different sizes. SP-A expression in small airways (<1 mm) was found to be 2.5 fold higher (p=0.018) in asthmatic airways than non-asthmatic airways. SP-D expression was found to be significantly higher (p<0.004) in asthmatic airways. In the ALI cultures, RSV infection induced a marked reduction in SP-D expression however, pre-treatment with conjugated linoleic acid (CLA) prior to RSV infection showed a 3.8 fold increase (p<0.05) in SP-D expression compared to RSV infection alone. Sucrose gradient fractions of protein lysates showed SP-D proteins in non-lipid fractions.

CONCLUSIONS:

Our data demonstrates surfactant proteins are expressed differently in the airways of asthmatics. The increased SP-A and SP-D detected in the asthmatic airway may reflect an increased susceptibility to viral infections due to dysregulated protein expressions, dysfunctional protein products, or chronic injury of airway tissue and requires further study.

Footnotes

Funding: CIHR: Allergen, NCE

Can Respir J. 2012 May-Jun;19(3):e35.

7: Comparison of miRNA Expression Profiles in Peripheral Blood of Early and Dual Responders Undergoing Allergen Inhalation Challenge

Masatsugu Yamamoto 1,2,3,4, Amrit Singh 1,2, Jian Ruan 1,2, Gail M Gauvreau 5, Paul M O’Byrne 5, Chris Carlsten 2,3,4, J Mark FitzGerald 2,3,4, Louis-Philippe Boulet 6, Scott J Tebbutt 1,2,3

Abstract

RATIONALE

The early and late responses can be detected in atopic asthmatic undergoing allergen inhalation challenge (AIC). MicroRNAs (miRNAs) are small non-coding RNAs that can bind to multiple target mRNAs to regulate protein production. While some miRNAs have been reported to be dysregulated in some diseases, changes of miRNA profiles in blood cells of early responders (ERs) and dual responders (DRs) undergoing AIC have not been studied. We have investigated cellular miRNA profiles in whole blood in atopic asthmatics undergoing AIC.

METHODS:

Four ERs and four DRs participated in the ethically approved AIC. Venous blood was collected (EDTA tubes) immediately prior to challenge (pre) and 2 hours post-challenge. Total RNA was extracted using a Qiagen miRNA mini kit. A total of 734 miRNAs derived from miRBase were profiled using the nCounter Expression Assay (NanoString Technologies, Seattle). After data processing and initial filtering, moderated robust regression in R (statistical computing program) was used to assess differential (FDR=10%) expression of miRNAs. Ingenuity Pathway Analysis (IPA) was used to determine top biological functions.

RESULTS:

A total of 149 miRNAs were expressed across all samples; 242 miRNAs were below the detection threshold for all samples. A total of 48 (16 up- and 32 down-regulated) differentially expressed miRNAs were identified in the pre vs. post comparison in ERs. However, only one miRNA was differentially expressed in the pre vs. post comparison in DRs. The top biological functions identified using IPA for post- compared to pre-challenge in ERs included Inflammatory Disease, Connective Tissue Disorders, and Respiratory Disease.

CONCLUSION:

Significant changes in miRNA levels can be detected in peripheral blood following AIC. These changes are more significant in ERs than DRs. This study shows the use of the AIC in order to improve understanding of regulatory mechanisms in asthma.

Footnotes

Financial support: AllerGen NCE Inc. (Allergy, Genes and Environment Network); Canadian Institutes of Health Research

Can Respir J. 2012 May-Jun;19(3):e35.

8: Dysregulated Expression of IL-13 Receptors in the Asthmatic Airway Epithelium

Jasemine S Yang 1, Angela Saunders 1, Sima Allahverdian 1, Samuel J Wadsworth 1, Gurpreet K Singhera 1, Delbert R Dorscheid 1

Abstract

RATIONALE

The airway epithelium serves as a defense barrier and suffers frequent injury as a result, requiring repair coordinate with inflammation. Interleukin-13 (IL-13) is known to be a key cytokine in mediating inflammatory and remodelling processes in asthma. The actions of IL-13 are mediated by IL-13 receptor α1 (IL-13Rα1) and IL-13 receptor α2 (IL-13Rα2). Our lab has demonstrated that IL-13 is critical to normal airway epithelial repair via signaling the release of HB-EGF and activation of EGF-R. Appropriate control of inflammatory and repair processes is tightly regulated by the balance of IL-13Rα1 and IL-13Rα2 expression and function in response to injury.

AIM:

To investigate the expression of IL-13Rα1 and IL-13Rα2 in normal and asthmatic airways.

METHODS:

Expressions of IL-13Rα1 and IL-13Rα2 in sections from normal and asthmatic lung tissue were determined via immunohistochemistry and quantified using ImagePro Plus. Primary airway epithelial cells (AEC) from normal and asthmatic donors were cultured in monolayers and subjected to mechanical wounding and IL-13 stimulation over a time course of 24 hours. The cultures were then lysed for protein and RNA extraction and IL-13Rα1 and IL-13Rα2 levels were detected via Western blotting and qRT-PCR respectively.

RESULTS:

Immunohistochemical detection demonstrated that asthmatic airways, specifically in the epithelium expressed significantly (p<0.05) higher levels of IL-13Rα1 compared to normal donors. Asthmatic airways also do not express significant levels of IL-13Rα2 and exhibit epithelial abnormalities. Cultured monolayer AEC from asthmatic donors continue to secrete IL-13 in excess relative to normal AEC. In addition to dysregulated IL-13 release, these cells demonstrate abnormal IL-13Rα2 expression and function with markedly impaired repair.

CONCLUSION:

Our data indicates that expression of IL-13 receptors is dysregulated in the airways of asthmatics and this contributes to the dysfunctional repair phenotype observed in the asthmatic epithelium.

Footnotes

Funding: AllerGen-NCE, CIHR

Can Respir J. 2012 May-Jun;19(3):e35–e36.

9: Optimal Fixed Cut-Offs for FEV1/FEV6 as Alternatives for FEV1/FVC for Detection of Airway Obstruction – Results from the Population-Based Canadian Obstructive Lung Disease (COLD) Study

Junior Chuang 1, WC Tan 1, J Bourbeau 2, P Hernandez 3, K Chapman 4, R Cowie 5, MJ FitzGerald 6, S Aaron 7, DD Marcinuik 8, F Maltais 9, DE O’Donnell 10, R Goldstein 11, D Sin 1

Abstract

BACKGROUND

The ratio of forced expiratory volume in one second to that in 6 seconds FEV1/FEV6, has been suggested as a surrogate for FEV1/forced vital capacity(FVC) for screening airflow obstruction.

AIM:

The purpose of the study is to determine the optimal fixed cut-off points for FEV1/FEV6 as an alternative to FEV1/FVC in the detection of spirometric obstruction.

METHODS:

3,042 people aged 40 years and older from 5 sites in Canada completed interviewer administered questionnaires and performed spirometry before and after administration of 200ug of inhaled salbutamol (albuterol). The data from 2911 [96%] subjects with ATS acceptable spirometric data on bronchodilator response, was used for analysis. The cutoff value for FEV1/FEV6 with the best sum of sensitivity and specificity was determined from receiver operating characteristics (ROC) curves.

RESULTS:

FEV1/FEV6 <77% was the best cut-off that corresponded to fixed ratio FEV1/FVC <70%, while FEV1/FVC<75% matched lower limits of normal (LLN) FEV1/FVC for detection of airflow limitation, as determined from the ROC curves shown below. The sensitivity, specificity for FEV1/FEV6<77% cut-off were: 94.3%, 87.0% respectively; the corresponding values for FEV1/FEV6 <75% cut-off were: 91.4%, 91.6%.

graphic file with name crj19e0312.jpg

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CONCLUSIONS:

Optimal fixed cut-offs of FEV1/FEV6 can be used as valid substitutes to FEV1/FVC fixed ratio or FEV1/FVC LLN, respectively in the screening of airflow limitation in unselected general populations.

Footnotes

Funding: Support for the COLD(CanCOLD) study was provided by unrestricted educational grants from AstraZeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Pfizer Canada and CIHR Rx&D Collaborative Research Program.

Can Respir J. 2012 May-Jun;19(3):e36.

10: Simple Spirometry as a First Line Test for Asthma Diagnosis in Primary Care

Anthony D’urzo 1

Abstract

RATIONALE

Spirometry is recommended as a first line test for asthma diagnosis in a number of guidelines. The present study was undertaken to determine whether there is sufficient evidence to promote spirometry as a first line test for asthma diagnosis in primary care as compared to MCT.

METHODS:

Medline/Embase were used (search words, spirometry, bronchodilator responsiveness (BDR), asthma diagnosis, methacholine challenge testing, comparison, sensitivity, specificity) to identify articles comparing BDR using simple spirometry to MCT in the primary care setting. There were insufficient randomized-controlled studies with comparable design, patient populations and outcomes to carry out a systemic review or meta-analysis. A critical analysis of relevant publications was carried out.

RESULTS:

The available publications reviewed suggest that MCT has far greater sensitivity for asthma diagnosis (among primary care patients) compared to BDR using simple spirometry. In fact, most asthma patients in primary care present with normal baseline spirometry on initial testing; few studies describe practical strategies for spirometric asthma diagnosis and management when initial spirometric testing is normal.

CONCLUSIONS:

This study suggests that asthma diagnosis can be confirmed in only a small minority of patients using simple spirometry and BDR compared to MCT. The current evidence does not support simple spirometry as a first line test for asthma diagnosis in primary care. Further studies comparing simple spirometry to MCT for asthma diagnosis confirmation and de-novo asthma diagnosis in primary care are required. Such studies should also address practical considerations related to how test selection may influence costs and outcomes related to asthma care. Current Canadian asthma guidelines should highlight the low sensitivity of simple spirometry for asthma diagnosis compared to MCT, including practical strategies designed to promote management of patients in the interim between suspected and confirmed asthma diagnosis.

Can Respir J. 2012 May-Jun;19(3):e35.

11: The Association of Asthma Education Centres on Repeat Hospitalizations and Emergency Department Visits for Asthma in Ontario

Nancy J Garvey 1,2, Yan Lu 2, Jun Guan 2, Phillip T Bwititi 1, Therese Stukel 2,3,4, Astrid Guttmann 2,3

Abstract

RATIONALE

Clinical practice guidelines for asthma recommend patient education as an essential component of optimal asthma management. Since 1990, over 30 hospital-based asthma education centres (AECs) have been established in Ontario. This study investigated whether access to AECs by patients in Ontario is associated with reduced risk of asthma readmissions and repeat emergency department (ED) visits.

METHODS:

This retrospective population-based cohort study using linked health administrative and survey data included all children and adults aged 2 to 55 hospitalized or admitted as high triage score ED attendees with a diagnosis of asthma in Ontario from April, 2004 to March, 2007. Poisson regression modeled the effect of AEC availability at the index hospitalization or ED visit (none, part-time, full-time and extended hours) controlling for age, gender, socioeconomic status, rural residence, history of prior asthma admissions, primary and/or specialist asthma care, and hospital type on outcomes: readmissions or high triage ED visits or death in the 6 to 36 months following the index event.

RESULTS:

Of the 163 acute care facilities in Ontario included in the study, 36 had hospital-based AECs and 17 others provided referral service to a hospital-based site. 75,054 children and adults who had been hospitalized or admitted to the ED were included in the cohort. There was a significant decrease in repeat ED visits for patients who had access to an AEC that offered extended hours (mean estimate 0.7831, 95 percentile confidence intervals 0.68–0.90, p=0.0003) as compared with those with no access to AEC. There were no significant advantages to patients with access to AECs with limited or part-time hours.

CONCLUSIONS:

As currently implemented in Ontario, access to AECs is only associated with measurable benefit if AECs offer fulltime regular and extended hours. Implementation of AECs should consider availability of services.

Footnotes

Funding: Grant from the Canadian Institutes for Health Research

Can Respir J. 2012 May-Jun;19(3):e36–e37.

12: Valved Holding Chambers (VHCS) are Non-Interchangeable: Development of a Universal VHC that Provides Assurance of Drug Delivery to Patients and Health Care Providers

H Harkness 1, C C Doyle 1, R Ali 1, V Avvakoumova 1, J P Mitchell 1, MW Nagel 1

Abstract

RATIONALE

Achieving compliance with inhaled therapy is challenging. Developing patient friendly VHCs that provide feedback of proper use (example, Inspiratory Flow Indicator) can help on the patient side. However, practitioners need security in knowing that the VHC prescribed will not impact the amount of inhaled drug delivered. Each pMDI+VHC combination is unique and only chambers that have been tested with a particular inhaler should be recommended. This laboratory investigation was undertaken to assist practitioners in the pMDI+AS-VHC selection.

METHODS:

AeroChamber® Girlz/Boyz® VHCs (Trudell Medical International, London, Canada) manufactured from non-conducting materials were evaluated with several pressurized metered-dose inhaler (pMDI) products (n=5 devices/group). VHCs were prepared in accordance with manufacturer instructions. Measurements of fine particle mass <4.7 μm aerodynamic diameter (FPM <4.7μm) were made at 28.3 L/min by Andersen multi-stage cascade impactor (ACI) equipped with USP/Ph.Eur. induction port operated with a 2 s delay interval between pMDI actuation and the onset of sampling, simulating use by an uncoordinated patient. FPM <4.7μm was also determined for the pMDI alone (no delay). Assay for the active pharmaceutical ingredient(s) recovered from the components of the measurement apparatus was undertaken by validated methods based on HPLC-spectrophotometry.

RESULTS:

FPM <4.7μm for the pMDI alone and pMDI+AS-VHC (mean ± S.D.) respectively are summarized for the following pMDI products: Flovent®-125: 46.2±2.1, 44.7±2.8; Ventolin®: 34.8±1.4, 33.4±4.2; Advair®50/25 – fluticasone propionate component: 17.4±2.1, 19.7±1.0; Advair®50/25 – salmeterol xinafoate component: 8.9±1.3, 9.5±0.6; Atrovent®: 6.7±0.4, 7.1±0.7; Alvesco®:99.9±2.5, 97.1±6.1; Qvar™: 41.9±2.2, 42.6±5.7; Zenhale® – mometasone furoate component: 43.8±1.7, 41.9±3.5; Zenhale® – formoterol component: 2.4±0.3, 2.0±0.1.

CONCLUSION:

The AeroChamber® Girlz/Boyz® VHC can be used with the pMDI medications studied without modifying prescribing instructions, as the pMDI alone and pMDI+VHC drug delivery are substantially equivalent.

Footnotes

Financial support: The authors are employees of Trudell Medical International, who funded the study.

Can Respir J. 2012 May-Jun;19(3):e37.

13: Impact in Healthcare Service use of Asthma Patient with Changing Medication Regimens – The Importance of Optimal Management

T Zhang 1,2, R Jimenez-Mendez 1,3,4, A Smith 3,4, B Carleton 1,2,3,4

Abstract

INTRODUCTION

Suboptimal medication regimen in Asthma is associated with a higher risk of exacerbations. Unfortunately, a substantial number of patients remain on suboptimal therapy. This study determined the association between changes of asthma drug therapy (i.e. suboptimal to optimal) and patients’ health service utilization over a nine-year period.

METHODS:

A cohort of 129,698 asthma patients between 5 and 55 years were identified using provincial health service utilization data between 1996 and 2004. The National Heart, Lung and Blood Institute Asthma Guidelines recommendations for optimal drug therapy were used to categorize patient-specific yearly regimens of short-acting bronchodilators with or without inhaled corticosteroids (ICSs) as optimal or suboptimal. Analyses focused on patients with nine suboptimal or optimal regimen years and patients with up to 7 suboptimal regimen years followed by 2 years of optimal regimens. Outcomes were the occurrence of asthma-related emergency department (ED) visits or hospitalizations during the suboptimal or optimal time period. Generalized estimating equation models were used for the analysis.

RESULTS:

Patients who used asthma medication suboptimally over the entire study period were six times more likely to use ED (OR 5.8, 95% CI 4.8–7.3) and eight times more likely to use hospital services (OR 8.3, 95% CI 5.3–13.1) for asthma compared to patients who used their medications optimally over 9 years. Patients who changed their drug therapy from suboptimal to optimal were significantly less likely to be admitted to ED or hospital for asthma compare to patients who used their medications suboptimally over the entire 9 years (e.g., among patients with 4 suboptimal regimen years followed by 2 optimal regimen years, OR 0.1, 95% CI 0.02–0.46).

CONCLUSION:

Changing from suboptimal to optimal therapy results in reductions in healthcare service use by asthma patients. Findings from this study suggest the need of close monitoring of patients’ therapy and encouraging adherence to guidelines.

Can Respir J. 2012 May-Jun;19(3):e37.

14: Asthma in Older Adults: Potential Factors to Explain the Increased Mortality Rates

Richard Leigh 1, Tony W Meng 1, Charity D Greene 1, Suzanne L Traves 1, Margaret M Kelly 1, David Proud 1

Abstract

RATIONALE

It is estimated that 7% of people over 65 have asthma. Of concern is that asthma-related mortality rates are about 10-fold higher in asthmatics over 65, compared to any other age group. The reasons for this difference are unknown and, in this study, we sought to test the hypothesis that airway inflammatory phenotypes in older adults with asthma differ from other age groups.

METHODS:

Induced sputum cell counts are performed on all patients attending our hospital-based asthma clinic to guide clinical management. Patient data, including medications, spirometry measurements and sputum cell counts are entered into an electronic database. We therefore performed a retrospective analysis of these data to determine the nature of the airway inflammation in patients > 65 years (older) compared to those under 65 (younger) with physician-diagnosed asthma.

RESULTS:

Between 2005 and 2011, 1046 patients with physician-diagnosed asthma had sputum analysis. Of these, 930 were under 65 and 116 were > 65 years old. The majority (75%) of older patients had sputum eosinophils >2.0%, vs. 54% of patients <65 (p<0.001). The median eosinophil count in the older group was 7% (IQR 1.5–31%) vs. 2% (0.3–9%) in the younger group (p<0.001). The older group had more severe airflow obstruction (FEV1 75% predicted) vs. the younger group (FEV1 85%) (p<0.001). There were no differences in treatment regimens between the 2 groups.

CONCLUSIONS:

Asthmatic patients over the age of 65 have a higher proportion of eosinophilic airway inflammation when compared to younger patients. This is despite the fact that both groups received similar treatment regimens. These results indicate that the asthma in the elderly is unlikely to be due to misclassification of COPD, and implies that elderly patients are either less adherent to current asthma therapies or that the underlying airway inflammation is relatively resistant to current anti-inflammatory therapies.

Footnotes

Funding: Alberta Health Services

Can Respir J. 2012 May-Jun;19(3):e37.

15: Asthma Control in a Random Sample of Canadian Asthma Patients

Mohsen Sadatsafavi 1, Roxanne Rousseau 2, Larry D Lynd 1, Carlo A Marra 1, Wan C Tan 2, Mark J FitzGerald 2

Abstract

INTRODUCTION

Asthma control has been documented as being suboptimal in many studies. The reported prevalence of asthma control has not always been population-based and may be severely biased by the sampling method.

METHODS:

We prospectively recruited subjects 1- to 85-years-old in British Columbia, Canada, using random digit dialing. Included subjects had a physician diagnosis of asthma with at least one asthma-related medical encounter in the past five years. At baseline we collected information on the demographic characteristics, socioeconomic status, did spirometry, and determined the level of asthma control according to the Global Initiative for Asthma (GINA) classification. We calculated the prevalence of controlled, partially controlled, and uncontrolled asthma. We also performed a proportional-odds ordinal logistic regression analysis with asthma control level as the dependent variable among the sub-sample of adolescents and adults for whom socio economic data were available.

RESULTS:

Control level could be assessed for 272 subjects (97% of sample, mean age 43.9 years, s.d. 21.0, 59.3% female). Of these, 67 (24.6%) were controlled, 109 (40.1%) were partially controlled, and 96 (35.3%) were uncontrolled. The Table shows the results of the regression analysis among the adolescent and adult asthmatics (n=232). The only two factors associated with the level of control were gender (p=0.05) and whether the patient was born in Canada (p=0.03). However, there was no association between these two factors (p=0.78 for gender, p=0.43 for place of birth) and asthma control among children (n=33) in the univariate analysis.

CONCLUSION:

Our results obtained from a random sample in BC showed a substantial lack of asthma control. There was no difference in the level of asthma control between sexes in children. However, among adolescents and adults, females had greater risk of poorer control. Our results may help policy makers with strategies for targeting populations to achieve better asthma control.

Can Respir J. 2012 May-Jun;19(3):e38.

16: Use of Complementary and Alternative Therapies in Patients with Asthma: Preliminary Results From a Prospective Study

Mohsen Sadatsafavi 1, Roxanne Rousseau 2, Larry D Lynd 1, Carlo A Marra 1, Wan C Tan 2, J Mark J FitzGerald 2

Abstract

INTRODUCTION

Asthma patients are using complementary and alternative therapies (CATs) in the management of their asthma. As part of an ongoing study, we prospectively documented participant reported use of CATs.

METHODS:

We recruited participants 1–85 years old from two geographic locations in BC using random digit dialing (RDD). Inclusion criteria were a physician diagnosis of asthma and use of at least one asthma-related health care resource in the past 5 years. We collected information on demographic characteristics, use of CATs, and performed a lung function test. Participants were categorized based on the level of asthma control (defined per GINA 2006 including lung function results). We compared the demographic information and asthma control of users and non-users of CATs.

RESULTS:

For 280 participants (99% of recruited sample) the data on CATs use was complete (mean age 43.6±20.4, 60.5% female) with 75 subjects reporting any CAT (26.8%) use. Common CATs were breathing exercises, and herbal medicines (11.1% each) and dieting (5.7%). Homeopathy was the least common form of CAT (1.8%). Among participants reporting use of CAT compared to non-CAT users there were no significant differences with age (p=0.44) and gender (p=0.33). There was a significant inverse association between use of AT and asthma control: among the users of CAT, asthma was fully controlled in 16.9% while in non-users it was fully controlled in 30.1% (p=0.03) according to GINA guidelines.

CONCLUSIONS:

Randomly selected participants showed poor asthma control where the use of CAT was high. The inverse relationship between the use of CAT and asthma control could be due to the complementary role of CAT among patients whose asthma is difficult to control despite medications, a substitute role among patients who are not willing to adhere to conventional therapies for their asthma, or even a potentially casual role in worsening asthma.

Footnotes

Financial support: Funding was obtained from the GlaxoSmithKline Collaborative Innovative Research Fund (CIRF).

Can Respir J. 2012 May-Jun;19(3):e38.

17: Do Hairdressers Experience More Respiratory Symptoms than Non-Hairdressers?

Shamara Sinnatamby 1,2, Dennell Mah 1, Jeremy Beach 1, Dilini Vethanayagam 1

Abstract

INTRODUCTION

Hairdressers may complain of general (headaches, dizziness) and respiratory (shortness of breath, cough, wheeze) symptoms with exposure to chemicals such as hair bleaches, dyes and styling products. As hairdressers are frequently exposed to chemicals, this suggests a possible association between the hairdressing occupation and asthma. This study aimed to investigate this association through the administration of a questionnaire to a group of hairdressers and a group of retail workers.

METHODS:

We conducted a cross-sectional study in the Edmonton area. Hairdressers and a comparison group of retail workers were chosen by convenience sampling and asked to complete a questionnaire which included questions about respiratory symptoms (and whether symptoms were experienced at work or not at work), family history of asthma, exposure to hair bleaches and dyes, asthma/allergy history and smoking history. Subject demographics including age, gender, education, occupation, years in current occupation were also recorded.

RESULTS:

55 hairdressers and 52 retail workers participated. The average age of the hairdressers was 29 years, the majority (85%) were female. Hairdressers interviewed had spent a mean of 8.8 years working in the industry. Average age of the retail workers was 23 years, the majority were female (67%). Retail workers had spent an average of 3.2 years in their occupation. There were statistically significant differences with hairdresser reporting more shortness of breath (p=0.04), cough (p<0.01), and dizziness (p<0.01) than retail workers. There were no differences in asthma or allergy history between the two groups. More hairdressers than retail workers reported eczema/dermatitis (p<0.01), but none of the hairdressers reported this developed after starting work in the industry.

CONCLUSIONS:

Significantly more respiratory symptoms were reported by the hairdresser group. There was no significant difference between the groups in reported asthma or allergies, while a difference in the prevalence of eczema/dermatitis may not be work-related.

Footnotes

Funding: No external funding

Can Respir J. 2012 May-Jun;19(3):e38.

18: Asthma and COPD Patients’ Care Gaps at Emergency Department Discharge

Cristina Villa-Roel 1,2, Mohit Bhutani 3, Jennifer Victor 1, Stephanie Couperthwaite 1, Brian H Rowe 1,2

Abstract

RATIONALE

Asthma and (chronic obstructive pulmonary disease) COPD patients who present to the Emergency Department (ED) usually lack adequate ambulatory disease control. There is limited information regarding the pharmacologic or non-pharmacologic needs of these patients at discharge. This study aimed to evaluate patients’ needs concerning the ambulatory management of their respiratory conditions after ED treatment and discharge.

METHODS:

Over 11 months, 108 adult patients with acute asthma or COPD, presenting to a tertiary care Alberta Hospital ED and discharged after being treated for exacerbations were enrolled. Using a standardized form, charts were reviewed by trained data abstractors to identify care gaps.

RESULTS:

Overall, 67 asthmatic and 41 COPD patients were enrolled. More patients with asthma required education on spacer devices (57% vs 32%; p=0.02). Most asthma (93%) and all COPD patients denied written action plans; however, asthma patients were more likely to need adherence counselling (51% vs 32%; p=0.08) for preventer medications. More patients with asthma required influenza vaccination (72% vs 37%; p=0.001); pneumococcal immunization was low (34%) in COPD patients. Only 22% of asthmatics reported ever being referred to an asthma education program and 20% of the COPD patients reported ever being referred to pulmonary rehabilitation. At ED presentation, 33% of the asthmatics were assessed to require the addition of inhaled corticosteroids (ICS) and 15% required the addition of ICS/long acting beta-agonist (ICS/LABA) combination agents. Conversely, 32% of COPD patients were assessed to require the addition of long acting anticholinergics (LAAC) while most (85%) were receiving preventer medications. Finally, 32% of COPD and 27% of asthma patients required smoking cessation counselling.

CONCLUSIONS:

Overall, we identified various care gaps for patients presenting to the ED with asthma and COPD. There is an urgent need for high-quality research on interventions to reduce these gaps.

Footnotes

Funding: Department of Emergency Medicine, University of Alberta; GlaxoSmithKline (GSK).

Can Respir J. 2012 May-Jun;19(3):e39.

19: Preventing Asthma Exacerbations with a Short Course of Oral Steroids at the Earliest Sign of Upper Respiratory Tract Infections: Preliminary Results of an Ongoing Policy Trial

B Wilkinson 1,2,3, R Jimenez-Mendez 1,2,3, G Groeneweg 1,2,3, A Smith 1,2,3, R Goldman 1,4, B Carleton 1,2,3

Abstract

RATIONALE

Emergency department (ED) visits due to asthma exacerbations account for a significant burden on health services, and affects the quality of life of patients and families. As much as 80% of these exacerbations are caused by upper respiratory tract infections (URTIs). Despite being recommended in clinical guidelines, prescribing a short course of oral steroids at the earliest signs of a URTI is still not widely accepted.

METHODS:

Repeated users of ED services with a diagnosis of asthma exacerbation are randomized either to receive a filled prescription of oral steroids with detailed instructions on how to use them at the earliest sign of their next URTI, or are provided with the standard of care upon departure from the ED. Follow up interviews are conducted to determine quality of life and the occurrence and frequency of any asthma exacerbations and/or URTI symptoms.

RESULTS:

We have enrolled 60 patients, with 19 in the intervention group. 6 patients in this group have used the provided oral steroids and were able to avoid further ED or Physician visits. A higher quality of life was reported also in this patients and families. Several factors have been identified as barriers: the believe that the families will not be able to correctly administer the oral steroid, that oral steroids will be administered but not followed up with correctly, and that there is no value in providing access to a medication when there is no active exacerbation.

CONCLUSIONS:

We have documented the efficacy of this intervention, and its positive impact on the quality of life for both patients and families. Some barriers that contribute to the difficulty in widely implementing this strategy into practice had been identified. Further research is necessary to quantify the improvement in quality of life, and to record barriers in uptake by different stakeholders.

Can Respir J. 2012 May-Jun;19(3):e40.

20: Klearway™ Oral Appliances for Pediatric Patients with Retruded Mandibles

H Chen 1, K Yagi 1, Hiroko Tsuda 2, F Almeida 3, A Lowe 1

Abstract

RATIONALE

The Klearway™ appliance was designed to open the airway by gradual advancement of the mandible. It has been used successfully for adult patients with obstructive sleep apnea and/or snoring. The functional effects of Klearway™ on mandibular growth in pediatric patients with retruded mandibles have not been investigated. This preliminary study assessed how Klearway™ could be utilized as a functional appliance.

METHODS:

Patients were selected to participate from the undergraduate orthodontic program at UBC. The criteria for each patient were: patients with mixed dentitions, significant overjets, growth remaining, well aligned lower incisors upright over basal bone and good lower face heights. The baseline data included study models, cephalometric & panoramic X-rays, together with intra-oral & extra-oral photos. In addition, a sleep questionnaire was administered at baseline. A customized Klearway™ was fabricated for each patient and a portable sleep monitor (Watch-Pat) was used on the insertion night. Patients were advised to wear Klearway™ at night only. The patients were treated by monitoring and/or adjusting Klearway™ on a monthly basis. Follow-up records were obtained to verify the craniofacial changes and sleep quality.

RESULTS:

No patients discontinued therapy due to appliance discomfort. Some 18 patients (8 girls and 10 boys) completed Phase I treatment. The average baseline age was 12 years 0 months. The Angle’s classification transitioned to Class I in 16 patients and Class III in 2 patients. The over-jet was significantly decreased from 7.0±2.4 mm to 3.0±2.3 mm (p<0.001). The overbite was decreased significantly from 59.4±23.6% to 28.1±19.4% (p<0.001). There were no significant findings in questionnaire scores and sleep analysis.

CONCLUSIONS:

Klearway™ is a suitable functional appliance for pediatric patients who exhibit retruded mandibles. This preliminary study did not confirm any significant changes in children’s sleep.

Can Respir J. 2012 May-Jun;19(3):e39.

21: Effect of an Integrated Care Approach with Self-Management in Patients with COPD

A Joubert 1, I Ouellet 1, I Drouin 1, C Lombardo 1, F Paquet 1, D Beaucage 1, J Bourbeau 1

Abstract

BACKGROUND

Most successful integrated care approaches include interdisciplinary care team and self-management preparation emphasizing the patients’ central role in managing their chronic disease.

OBJECTIVE:

To assess success of a customized self-management program (www.livingwellwithcopd.com Password: copd) with case management in COPD patients with increased disease severity from a COPD clinic i.e., patients’ use of the Action Plan in the event of an exacerbation.

METHODS:

Amongst patients who were followed in the COPD clinic program at the Montreal Chest Institute, 100 patients were randomly selected (50 in 2006 and 50 in 2009). The intervention includes an integrated care approach where the case manager plays a central role. An important component of the program is the self-management preparation including the written action plan. Data were collected from chart review over one year period: 2005–2006 and 2008–2009. Information included patient characteristics, nursing case management activities and action plan outcomes. Success of acute exacerbation self-management was defined with respect to: 1) patient behavior, i.e., patient’ use of the antibiotic and/or prednisone in the event of an exacerbation; 2) complication of exacerbations, i.e., health services use such as emergency room visits and hospital admissions.

RESULTS:

Overall patients had FEV1 of 1.0L in 2006 and 0.85L in 2009. In 2005–2006, 71% of patients used an action plan with self-administered prescription at least once compared to 87% in 2008–2009. The action plan for an exacerbation was used successfully in 53% of the events in 2006 and 64% of the events in 2009. In 2008–2009 only 5% of the events required an ER visit compared to 14% in 2005–2006.

CONCLUSION:

Despite the fact that patients had a more severe disease in 2009 as compared to 2006, they used their action plan in the event of an exacerbation more successfully and they had less visits to the ER.

Footnotes

Financial Support: Unrestricted educational grant from GSK.

Can Respir J. 2012 May-Jun;19(3):e39.

22: The Impact of Polypharmacy on the Outcomes of Pulmonary Rehabilitation

Eric Kaplovich 1, Roger S Goldstein 2, Robert G Varadi 2

Abstract

Polypharmacy, defined as the use of an excessive number of medications, has been associated with increased morbidity and drug side effects in several medical conditions. Although prevalent among patients with chronic lung diseases, its impact on pulmonary rehabilitation (PR) is unknown. We hypothesized that patients with polypharmacy enrolling in PR would experience less marked improvements in quality of life and exercise capacity than those without.

This retrospective cohort study included 299 patients (75% with chronic obstructive lung disease) who participated in a 6-week inpatient PR program in 2009–2010. Charts were reviewed for demographics, pulmonary function, exercise tests, symptoms and health status measures. All self-reported medications, including both prescription and over-the-counter products, were noted. Health status and exercise measures were repeated at program completion. The primary study outcome was change in the total Chronic Respiratory Questionnaire (CRQ) score.

RESULTS:

The median number of medications used was 10. Patients had severe lung disease (FEV1 44±21% predicted) and 23% required supplemental oxygen at rest. Patients with polypharmacy (using ≥10 medications) were older (70 versus 67 years, p=0.02) and had poorer baseline exercise tolerance (6-minute walk distance 257 versus 309 metres, p<0.01; self-paced endurance walk time 14 versus 18 minutes, p<0.01) than those without. Polypharmacy did not influence the post-rehabilitation change in CRQ (mean total CRQ score increased by 1.5 versus 1.3 units, p=0.17) or exercise tolerance (6MWD increased by 58 versus 54 metres, p=0.59), even when adjusted for age, sex, baseline lung function and exercise capacity.

CONCLUSION:

Polypharmacy did not adversely affect the improvements in health status or exercise tolerance following PR and should not prevent enrolment in PR.

Footnotes

Financial support: None.

Can Respir J. 2012 May-Jun;19(3):e40.

23: Respiratory Symptoms Associated with Chronic Conditions among Those with and without Asthma or COPD

Joshua Allan Lawson 1, Punam Pahwa 2, Shelley Kirychuk, Chandima Karunanayake, Donna Carole Rennie 3, Louise Hagel, James Dosman, on behalf of the Saskatchewan Rural Health Study (SRHS) Research Group

Abstract

BACKGROUND AND RATIONALE

Some chronic conditions may result from similar mechanisms suggesting the investigation of disease inter-relationships. We sought to determine if respiratory symptoms were more common among adults with chronic conditions and to examine this association among those with and without asthma or COPD.

METHODS:

We conducted a cross-sectional survey as part of the Saskatchewan Rural Health Study in 2010. Questionnaires were mailed to households in rural Saskatchewan. One adult per home provided information regarding each adult living in the home. There were 8261 adults from 4624 households (52% participation) included. Using descriptive statistics and multiple logistic regression, we examined the associations between reported diagnosed chronic conditions (diabetes, stroke, cardiovascular, chronic bronchitis, and sleep apnea) and respiratory symptoms (wheeze, cough, and phlegm) after adjusting for potential confounders and stratifying by history of doctor-diagnosed asthma or COPD.

RESULTS:

The respondents’ mean age was 56 years (SD=16 years) with 51% of the population being female. As expected, there was a higher prevalence (p<0.001) of reported wheeze, cough, and phlegm among those with a history of asthma or COPD (9.6% of the population). After adjustment, when there was no history of asthma or COPD, there was increased risk of wheeze associated with cardiovascular disease, chronic bronchitis and sleep apnea; increased risk of cough associated with each chronic condition except diabetes and; increased risk of phlegm with stroke, chronic bronchitis and sleep apnea. Among those with a history of asthma or COPD, respiratory symptoms were only associated with chronic bronchitis.

CONCLUSIONS:

Cardiovascular disease and stroke were associated with respiratory symptoms but only in the absence of asthma or COPD. Presence of these symptoms along with a non-respiratory chronic condition may result from common pathways, possibly inflammatory in nature, and may proceed more serious chronic lung disease.

Footnotes

Financial support: Canadian Institutes of Health Research (MOP: 90002)

Can Respir J. 2012 May-Jun;19(3):e40.

24: Perceived Needs of COPD Patients from Different Illness Severities Around the Approach to Advance Care Planning

A Joubert 1, M Nguyen 1, J Chamber-Evans 1, I Drouin 1, I Ouellet 1

Abstract

BACKGROUND

COPD’s unpredictable illness trajectory makes it difficult for patients to plan for the end-of-life (EOL). In studies, there is no clear consensus on what the needs for EOL would be, or under which conditions advance care planning (ACP) can be best approached with COPD patients. A DVD was developed in the province of Quebec as a tool for facilitating ACP.

OBJECTIVE:

The primary purpose of this study is to better understand the perceived needs of COPD patients from different illness severities around the approach to advance care planning (ACP). The secondary purpose is to investigate the usefulness of a DVD in meeting the needs of COPD patients at the Montreal Chest Institute.

METHODS:

A qualitative descriptive design is used to obtain rich data from 12 patients, four from each MRC categories 3, 4 & 5. Participants are recruited at the COPD clinic at the Montreal Chest Institute and are interviewed about their perceived needs on ACP. After viewing the DVD they participate in a second interview about their perceptions of it’s usefulness for approaching ACP.

RESULTS:

To date, 10 out of 12 patients were interviewed. So far, illness severity is not indicative of the amount of preparatory measures made for EOL. Half of the participants preferred ACP to be done sooner rather than later, while the other half did not want to have EOL approached at all until the very end. Moreover, no major differences in perceived needs appear between groups of illness severity. Regarding the DVD, subjects mainly appreciated patients’ testimonies.

CONCLUSION:

It seems that health professionals cannot rely on illness severity when initiating ACP with COPD patients and must remain sensitive to their personal values. A standardized approach to ACP may not be ideal. Rather, a patient-centered tailor-made approach would be more appropriate.

Footnotes

Financial support: None

Can Respir J. 2012 May-Jun;19(3):e40–e41.

25: Evaluating Impacts of a New COPD Outreach Program (INSPIRED)

Graeme M Rocker 1,2, Joanne Young 1, A Catherine Simpson 1, Jillian Demmons 1, Wendy Conrad 1

Abstract

RATIONALE

At the QEII HSC, COPD accounts for ∼ 300 admissions per year, costing ∼ $3 million annually. Current models of care, focused primarily on acute care, are failing with significant costs to patients, families, and systems. INSPIRED is a new evidence-based outreach program introduced to address gaps in care by providing holistic, hospital-to-home services for those living with advanced COPD. Services include: disease self-management education, creation of “action plans” for management of acute exacerbations, provision of psychosocial-spiritual support, and engagement of patients/family caregivers in advance care planning discussions.

METHODS:

For quality assurance purposes, a mixed-methods approach was used to evaluate the program’s initial phases. Patients (P) and family caregivers (FCG) were interviewed and completed quantitative measures for health-related quality of life and dyspnea intensity (P), anxiety/depression and hope (P; and FCG) before and after completion of the program. Interviews focused on the experience of living with advanced COPD, perceived gaps in care, and hopes for/views about INSPIRED. Using hospital databases, we also tracked patients’ COPD-related use of acute care services (number of ER visits and hospital admissions) from one year preprogram enrollment to 6 months following enrollment.

RESULTS:

From February to June of 2011, 27 patients were enrolled. Preliminary themes emerging from interviews suggests participants greatly appreciated the program and felt: 1) more confident in managing COPD-related symptoms, 2) less anxious/stressed, and 3) willing to discuss goals of care including those related to end-of-life. Changes to length of stay (LOS/Bed Days), ER visits, and estimated cost savings are outlined in Table 1.

Table 1.

Pre INSPIRED n=27 12 months Post INSPIRED n=27 Evaluation at 3 months Post INSPIRED n=27 Evaluation at 6 months Cost savings Post INSPIRED n=27 Projected at 12 months Cost savings Projected at 12 months
ER visits (n) 105 8 16 32
Admissions (n) 57 4 8 16
LOS/Bed Days 679 78 96 $487,000* 192 $974,000*
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*

Based on estimated cost of one bed day = $1000

CONCLUSIONS

Carefully planned chronic disease management initiatives can yield significant cost savings and decrease burdens for those living with advanced COPD.

Footnotes

Financial support: Pilot program: Hybrid funding. Program evaluation: Lung Association of Nova Scotia.

Can Respir J. 2012 May-Jun;19(3):e41.

26: Using Opioids to Treat Refractory Dyspnea in Advanced COPD: Early Insights from a Clinical Trial

Graeme M Rocker 1,2,3, Jillian Demmons 1, Margaret Donahue 1, Joanne Young 1, A Catherine Simpson 1, Paul Hernandez 1,3, Robert Horton 2,3

Abstract

RATIONALE

A 2011Canadian Thoracic Society (CTS) clinical practice guideline recommends opioids as a treatment for refractory dyspnea in patients with advanced COPD. However, experience with opioids in this setting remains limited and patient/family caregiver experiences are mostly unknown. We designed a clinical trial (NCT00982891) to further understand the experiences of those living with advanced COPD when opioids are added to optimized conventional treatment.

METHODS:

We conducted semi-structured interviews with patients (P)/family caregivers (C) before, at 2 months, and 4–6 months after initiating opioid therapy in addition to optimized conventional treatment. Interviews were recorded, transcribed verbatim, and analysed using interpretive description methodology. We also collected ratings of dyspnea, health-related quality of life (HRQoL) and how helpful (or not) participants found opioid therapy.

RESULTS:

38 patients have enrolled over 18 months, 28 (74%) have completed the trial (7 withdrawals, 3 deaths). Patient data at 2 weeks (n=31), 2 months (n=25), 4–6 months (n=20), describe opioids to be either very helpful (32%, 40%, 55%) or somewhat helpful (48%, 48%, 40%) respectively. Dyspnea intensity (Numerical Rating Scale 6.16 vs 4.76) and HRQoL (CRQ 3.4 vs 4.4) improved significantly (p<0.05) from baseline to 6 months respectively. Preliminary interview findings suggest opioids: 1) improve QoL; 2) provide a new sense of hope for the future; and 3) that positive impact of opioids may wane over time for some.

CONCLUSIONS:

Opioids, when carefully initiated and titrated, appear to be a helpful and acceptable intervention for refractory dyspnea with benefits sustained over months. Findings support recent CTS recommendations regarding opioid prescribing for refactrory dyspnea in advanced COPD.

Footnotes

Financial support: Canadian Institutes of Health Research

Can Respir J. 2012 May-Jun;19(3):e41.

27: Proteomic Signature in Plasma of Chronic Obstructive Pulmonary Disease Subjects can Differentiate Frequent Exacerbators from Non-Exacerbators

Karen Sherwood 1,2,3,4, Virginia Chen 3, Zsuzsanna Hollander 1,2,3,5, Janet Wilson-McManus 3, Bruce Miller 6, Bruce M McManus 1,2,3,5, Christoph H Borchers 7, Raymond Ng 1,2,3,8, Scott J Tebbutt 1,2,3,4, Don D Sin 1,2,3,4

Abstract

RATIONALE

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in Canada and may affect up to 3 million Canadians. COPD exacerbations are difficult to predict. To identify COPD subjects susceptible to exacerbations, and thus help COPD disease management, we aimed to discover a plasma proteomic profile that is predictive of frequent exacerbations.

METHODS:

A total of 166 subjects who had zero or one exacerbations in the year previous to enrollment were selected from the ECLIPSE cohort for the proteomics analysis. Of these, 107 were included for discovery (34 frequent exacerbators (FE) and 73 non-exacerbators (NE)) and 59 were included for validation (21 FE and 38 NE). Plasma samples were analyzed using iTRAQ-MALDI-TOF/TOF mass spectrometry. Data were interrogated using ProteinPilot™. Moderated robust t-test was used to determine differentially expressed proteins (p<0.1), which were used to build a classifier model using Elastic Net. Area under the receiver operating characteristic curve (AUC) and Net Reclassification Index (NRI) were used to compare the discriminative power of the panel with that of FEV1 and GOLD stage. UniProtKB was used to determine biological functions and canonical pathways.

RESULTS:

Eleven proteins were identified as significantly under-expressed in FE compared to NE samples. Of these, 4 proteins were included in the biomarker panel. The proteomic biomarkers were able to predict who will have frequent exacerbations in the next 3 years as well as FEV1 or GOLD stage (AUC = 0.71 versus 0.73 and 0.57 and NRI of −0.02 and 0.17 relative to FEV1 and GOLD stage respectively). UniProtKB suggests that the majority of these proteins are involved in biological processes such as cilium biogenesis, angiogenesis and innate immunity.

CONCLUSIONS:

Using an unbiased approach, we have identified differentially expressed proteins in plasma that separates COPD patients who will exacerbate from non-exacerbators. A protein biomarker panel has been constructed which performs similarly to FEV1 and GOLD stage as a predictor of future exacerbations.

Footnotes

Financial support: PROOF Centre of Excellence

Can Respir J. 2012 May-Jun;19(3):e41–e42.

28: Diabetes Mellitus and Pulmonary Function in Hospitalized Patients with Acute Exacerbation of COPD

Carmen A Sima 1, Satvir S Dhillon 1, Pat G Camp 1,2

Abstract

RATIONALE

Chronic Obstructive Pulmonary Disease (COPD) is an important cause of morbidity and mortality in elderly people, and multiple comorbid conditions significantly contribute to the burden of this disease. Diabetes Mellitus (DM), as a comorbid condition, is inconsistently associated with worse pulmonary function in COPD. In addition, corticotherapy and antipsychotic medication commonly used by COPD patients can affect blood glucose. This study investigates the relationship between DM and pulmonary function in patients hospitalized for an acute exacerbation of COPD (AECOPD). Secondary objectives include assessing the relationships between DM and typical COPD characteristics and treatments.

METHODS:

The charts of 88 patients with an AECOPD, admitted to St Paul’s and Mount St Joseph’s Hospitals between January 2008 and December 2010, were reviewed. The data included anthropometric characteristics, respiratory function, blood tests, presence of comorbidities, and prescribed treatment. A stepwise multivariate analysis was performed to assess the effect of DM on pulmonary function in AECOPD patients, adjusting for age, presence of cardiovascular disease, and smoking history.

RESULTS:

The mean age of AECOPD patients was 70±11 years with a 2:1 male/female ratio. FEV1 was 39±16% predicted. DM and cardiac diseases were present in 24% and 66% of patients with AECOPD, respectively. Body mass index (BMI) and casual glycemia were significantly higher in the diabetic group (33.7±9.5; 10.3±4.7 mmol/L) than in the nondiabetic group (24.2±6.7; 7.2±1.4 mmol/L). There was no difference in lung function between the two groups. Although corticotherapy and antipsychotic medication use was prevalent, there was no association between these therapeutic interventions and diabetes.

CONCLUSIONS:

The findings of this study suggest that DM does not influence lung function in elderly people with AECOPD; instead other factors may play an important role in this detrimental association.

Footnotes

Financial support: None disclosed

Can Respir J. 2012 May-Jun;19(3):e42.

29: Prevalence of Unrecognized Osteoporosis among COPD Patients

Ashley Smith 1, David Kendler 1, Mark FitzGerald 1

Abstract

BACKGROUND

COPD and oral glucocorticoids (OCS) are established risk factors for osteoporosis (OP) and fragility fracture. OP is underdiagnosed and undertreated in these patients.

AIM:

To evaluate the prevalence of low bone density and fragility fracture among patients with COPD seen in a Vancouver respirology clinic.

METHODS:

We invited COPD patients over 65, who had not had a bone density test in the prior 2 years, to participate in our observational study. Patients were attending a respirology clinic and all had a diagnosis of COPD. We collected spirometry and historical risk factors for OP including prior fracture and oral corticosteroid (OCS) use. We performed Bone Mineral Density by Dual Energy Xray Absortiometry (DXA) of hip and spine, Vertebral Fracture Assessment (VFA) and chemistries including serum 25-OH Vitamin D.

RESULTS:

The initial 15 patients (10 male and 5 female) exhibited all stages of COPD, mild COPD was diagnosed in one patient, moderate in four patients and 10 exhibited severe COPD. All but two patients were on inhaled combination therapy. OCS use was reported for 6 patients in the prior year. Normal bone density (T-score >−1) was found in one of the patients and osteopenia (T-score −1 to −2.5) was diagnosed in 4 patients. OP by DXA was found in 10 patients and VFA revealed vertebral fractures in 8 of these patients.

CONCLUSION:

COPD patients attending a respirology clinic have many risks for fragility fracture, including OCS use. They have a high likelihood of having low bone density and spine fracture. Guidelines encouraging the routine evaluation of bone health in COPD patients are required.

Footnotes

Funding: There has been no financial support for this project.

Can Respir J. 2012 May-Jun;19(3):e42.

30: Feasibility and Acceptability of a Community-Based Maintenance Exercise Program for People With COPD

Marla K Beauchamp 1,2, Susan Francella 3, Debbie Rolfe 4, Barbara E Gibson 5, Roger S Goldstein 2,5,6, Dina Brooks 1,2,5

Abstract

RATIONALE

Pulmonary rehabilitation (PR) improves exercise capacity and quality of life in individuals with COPD. However, following completion of PR, benefits diminish over time such that outcomes return to pre-intervention levels within 12 months. The purpose of this study was to describe the development, implementation and acceptability of a community-based maintenance exercise program for people with COPD post-PR.

METHODS:

A community-based exercise program was developed in partnership with the City of Toronto, Parks and Recreation. Individuals with COPD who recently completed PR were recruited to participate in a twice weekly exercise program at a local community centre supervised by a trained fitness instructor. The transition from hospital-based PR to the community centre was facilitated by a Physiotherapist. To explore patient perceptions of the program, three focus groups were conducted with 12 patients with COPD who had participated in the program for greater than six months. Focus groups were conducted by an experienced facilitator using a semi-structured interview guide. Interviews were audiotaped, transcribed verbatim and analyzed for recurring themes.

RESULTS:

Analysis of the data revealed four main findings: 1) Participants overwhelmingly endorsed the benefits of the program, particularly with respect to perceptions of improved functioning and endurance; 2) The main barriers to participant attendance were related to exacerbations, fatigue, weather and mood; 3) Attendance enablers were the existence and structure of the program, and feelings of accomplishment and improved quality of life; and 4) The most frequently cited recommendation was to expand the number of locations in which the program was held.

CONCLUSIONS:

The findings of this study suggest that participants found this intervention to be beneficial and recommended expansion to other sites. The potential value of community-based maintenance exercise programs for people with COPD warrants further exploration.

Footnotes

Financial Support: Marla Beauchamp is supported by the Canadian Institutes of Health Research and Dina Brooks is supported by a Canada Research Chair.

Can Respir J. 2012 May-Jun;19(3):e42–e43.

31: Physical Exercise, Our Tool

Clarisa Boim 1, Fernanda Monti 1, Sandra Chiervo 1, Miguel Storni 1, Marta Cortiñaz 1

Abstract

RATIONALE

The fitness results in Pulmonary Rehabilitation are not always completely achieved. This is the consequence of the subject with COPD characteristics and the available resources. However through our experience we were made to see the improvement in quality of life in our patients.

METHODS:

Between January 2010 and May 2011 we implemented a multidisciplinary Respiratory Rehabilitation Program, designed in three Stages: 1) initial assessments 2) general aerobic endurance, global and segmental strength, and flexibility during 32 sessions under supervised twice a week stimuli; and 3) reassessment. During the program 102 patients were interviewed: 32 patients (31%) completed all 3 stages. Of these patients, 15 (46,87%) were female and 17 (53,12%) were male; 32 (100%) had COPD. According to the GOLD classification, 16 patients (50%) were stage II, 11 (34,37%) stage III and 5 (15,62%) stage IV. Mean age was 66 years [SD ±7,4] and FEV1 was 1.25 l. [SD ±0,57]. Regarding BMI, 5 patients (15,62%) were underweight, 9 patients (28,12%) had normal weight, 10 (31,25%) were overweight and 8 (25%) were obese.

RESULTS:

Patients were reassessed upon completing the 32 sessions. CRQ results showed improvements in all four domains: Dyspnea, 21 patients (65,62%); Fatigue, 26 patients (81,25%); Emotional Function, 21 patients (65,62%) and Mastery 17 patients (53,12). As for the 6MWT, 18 patients (56,25%) achieved the MID (54 mts). Fourteen patients did not: 93% had improved in Fatigue, whereas 50% had improved in Dyspnea; 8 patients had a 6MWT >80% of predicted values per Enright’s formula, 2 had peripheral polyneuropathy affecting the lower limbs and 1 depressive syndrome.

CONCLUSIONS:

According to our experience, compliance improved over the last years (25% in 2004 vs. 31% currently). In our groups, the female population with COPD increased 50% over the last years. Patients are being referred at earlier GOLD stages, probably due to an increased promotion of PR. A review of patients show that over 50% are overweight. The improvement in the Fatigue domain (81,25%) – that implies an improvement in fitness – allows us to infer that the basis training was satisfactory, whereas the results of the 6MWT suggest the specific training was insufficient, although this could be due to the characteristics of this 14-patient population, and also to the fact that bicycles were used instead of treadmills for the GAE training.

Can Respir J. 2012 May-Jun;19(3):e43.

32: Eccentric Cycle Exercise for Patients with Severe COPD: Training Application and Feasibility

Riany de Sousa Sena 1, Jacinthe Baril 1, Danielle Soares Vieira Rocha 2, Ruddy Richard 3, Helene Perrault 1, Tanja Taivassalo 1, Jean Bourbeau 4

Abstract

RATIONALE

Considering that with eccentric training patients can sustain more muscle overload for a similar ventilatory demand, this training may be ideal for severe COPD patients who may not otherwise achieve intensities sufficient to induce physiological adaptations in skeletal muscle. However, evidence regarding the feasibility of high intensity eccentric exercise for COPD patients is lacking.

OBJECTIVES:

To examine the feasibility of a high-intensity eccentric cycling protocol for patients with COPD and to compare the effects of CON and ECC cycle on patients’ aerobic capacity (peakVO2).

METHODS:

In this pilot randomized control trial, 8 male patients with severe COPD (Age 67±6 years; FEV1 of 44±9 %predicted) were randomly assigned to either a CON (n=4) or ECC (n=4) cycling protocol over a course of 10 weeks. In order to monitor muscle injury, levels of serum creatine kinase were measured throughout the training period. The study was approved by the institutional ethics review board and all patients signed a informed consent.

RESULTS:

Subjects in the ECC group reached an average of 160±55 watts at 80±1.12% of peak heart rate while patients in the CON group exercised at 66 ± 16.6 watts at 92±1.7% peak HR. Scores of dyspnea for the ECC group were significant lower (median [IQR], 1.9 [1.7–2] compared with those in the CON group (median [IQR], 2.8 [2.4–2.9]; p<0.05), but no significant differences were found for the for leg fatigue between the two groups (median [IQR], CON, 3.0 [2.5–3.2]; ECC, 2.6 [2.4–2.7]). Levels of creatine kinase remained within the normal range after 5 and 10-weeks of training. Additionally, increases in peak VO2 were detected in both groups (ECC = 28%; CON=21%; p>0.05), although not statistically significant (p>0.05)

CONCLUSION:

Preliminary results showed that high intensity eccentric cycle exercise is feasible for patients with severe COPD. However, in this ongoing research, more patients have been included to investigate the potential benefits of eccentric training on the maximal exercise capacity of COPD patients.

Footnotes

Financial support: Riany de Sousa Sena is a PhD candidate supported by Edith Strauss fellowship in Rehabilitation Science.

Can Respir J. 2012 May-Jun;19(3):e43–e44.

33: Factors Associated with Low Six Minute Walk Distance in Advanced Cystic Fibrosis

Satvir S Dhillon 1,2, Robert D Levy 3, Pearce Wilcox 4, Carol Storseth 5, Isabelle Castell 5, Pat G Camp 1,6

Abstract

RATIONALE

Cystic fibrosis (CF) patients are referred for lung transplantation (LTx) assessment when they have a 2–3 year mortality risk greater than 50% and/or poor level of function as indicated by various measures, such as the 6 minute walk test (6MWT). It has been suggested that patients who walk less than 400m in the 6MWT should be listed for LTx. There is little understanding regarding the factors associated with low 6MWT for advanced CF patients.

METHODS:

The medical records of a sample of CF patients referred for LTx assessment were reviewed. Patient demographics, lung function, Lung Allocation Score (LAS), blood chemistry, heart rate and oxygen saturation at rest and during exercise, and anthropometric data was compared between patients with a 6MWT <400 m (Group A) or >400 m (Group B).

RESULTS:

Data from 20 patients (65% male) were collected. The mean(SD) 6MWT in Group A was 306.3(59.9) m; Group B 489.6(101.3) m. There was no difference in age, body mass index, LAS, PCO2, or PO2 between the two groups (p>0.05). Despite having similar lung function (Group A FEV1 % predicted: 29.1(5.1)%; Group B 27.4(10.6)%; p=0.65) and BMI (Group A 20.9(2.3)kg/m2; Group B 20.3(3.3) kg/m2; p=0.64), Group A had a significantly higher maximal heart rate during 6MWT (132.6(11.5) bpm compared to 109.7(19.6) bpm; p=0.04). The Group A resting heart rate was also elevated (102.4bpm), however this was not significantly different than Group B (88.6 bpm).

CONCLUSIONS:

The elevated maximal heart rate during 6MWT in CF patients who achieved a distance of less than 400 m may indicate a poor level of fitness in this group, and provides important information for the design of a prospective study on fitness and activity in these patients.

Footnotes

Financial support: None disclosed.

Can Respir J. 2012 May-Jun;19(3):e43–e44.

34: Arm Elevation and Coordinated Breathing Strategies in Patients with Severe Chronic Obstructive Pulmonary Disease (COPD)

Thomas E Dolmage 1,2, Tania Janaudis-Ferreira 2, Kylie Hill 2,3, Shirley Price 4, Dina Brooks 2,5, Roger S Goldstein 1,2,4,6

Abstract

BACKGROUND

Hyperinflated patients with severe COPD breathe against a high elastic load which increases further during the ventilatory demand of physical activity. Arm activities are especially demanding. Some pulmonary rehabilitation programs instruct patients to exhale while raising their arms whereas others recommend the opposite. The aim of this study was to determine the effect of co-ordinating breathing with arm movements on arm lift tolerance. We hypothesized that coordinating inspiration with arm elevation would increase the endurance time of a rhythmic lifting task.

METHODS:

Participants with COPD and resting hyperinflation completed two separate (low and high intensity) rhythmic constant load arm elevation tasks to intolerance (tlimit) before and after attending four “teaching” sessions (intervention). All patients were taught to extend expiration to achieve an expiratory: inspiratory ratio of 2:1. Participants were randomly assigned a group taught to lift during: 1) inhalation; 2) exhalation; 3) without constraint (sham).

RESULTS:

29 participants (FEV1 [SD] = 36 [16] %predicted, FEV1/FVC = 34 [12] %; TGV = 172 [39]) completed the study. There was a significant effect of GROUP on the change in tlimit (p<0.001) regardless of whether the test was done at low or high intensity (p=0.37). The Δtlimit in the ‘exhalation’ group was significantly greater than the ‘sham’ group at both low (difference [95%CI] = 281 [41 to 520] s) and high (difference = 214 [82 to 345] s) intensities. There was no difference in Δtlimit between the ‘inhalation’ and ‘sham’ groups.

CONCLUSION:

Teaching patients with COPD to coordinate exhalation with raising their arms increases the endurance time of a rhythmic lifting task. Coordinating inhalation with raising their arms does not affect endurance time. Therapists teaching arm lifting activities should co-ordinate them with exhalation to improve task endurance.

Footnotes

Funding: Canadian Respiratory Health Professionals (CRHP)

Can Respir J. 2012 May-Jun;19(3):e44.

35: Investigation of a Simple Method to Set the Walking Speed for the Assessment of Ambulatory Oxygen in Patients with Chronic Lung Disease

Thomas E Dolmage 1,2, Rachael A Evans 2, Nina Malek 2, Lauren O’Brien 2, Roger S Goldstein 1,2,3

Abstract

INTRODUCTION

Guidelines for assessment and qualification for ambulatory oxygen vary. A constant-speed endurance walk is the most responsive test. Conventionally its speed is individualized using an incremental walk test; an alternative is the average speed (s6MWT) of the six minute walk test (6MWT). We evaluated a simpler, less demanding, method to estimate the individual endurance speed.

OBJECTIVES:

To determine the point between patients’ usual (susual) and fast (sfast) walk speed resulting in the highest proportion of ‘ideal’ results for the assessment of ambulatory oxygen.

METHODS:

A chart review was conducted including all patients with chronic lung disease assessed for ambulatory oxygen where the susual and sfast were measured. The control (air) test speed was guided by their s6MWT. The ideal endurance time (tlimit) was defined as 5 to 16 min based upon Ontario’s Home Oxygen Program criteria.

RESULTS:

35 patients (mean [SD]: age = 70 [9] y; 6MWT distance = 336 [121] m; end exercise SpO2 = 81 [7] %) were included. The s6MWT, susual and sfast were 56 [20], 53 [15] and 72 [17] m•min-1, respectively. The speed of the control endurance walk test, breathing air, was 67 [16] m•min-1 resulting in a tlimit 5.6 [3.3] min. There was a poor relationship between s6MWT and tlimit (r=0.22; p=0.23); 40 % of tests resulted in an ‘ideal’ tlimit. Referring to the susual and sfast as 0 and 100 %, respectively, the mean endurance speed occurred at 79 [20] %. The majority of ‘ideal’ tests occurred at 65 to 85 % between susual and sfast.

CONCLUSION:

The 6MWT was of little help to the administrator in achieving a tlimit within the most responsive range. In contrast, the usual and fast walks provide a quick, simple, effective and inexpensive approach to estimating the speed for assessing ambulatory oxygen.

Can Respir J. 2012 May-Jun;19(3):e44–e45.

36: Home-Based Exercise Programming in Pulmonary Rehabilitation: A Case Report of A New Approach

Ray Down 1, Jamie Farrell 1

Abstract

RATIONALE

Home-based pulmonary rehabilitation is recommended as an equally effective alternative to hospital-based programming. Exercise training is an essential component of a pulmonary rehabilitation program. Eastern Health Pulmonary Rehabilitation launched an individualized, direct-to-home exercise pilot project in 2010.

This case report outlines a new approach of home-based exercise programming for a patient with chronic obstructive pulmonary disease (COPD) at our site.

METHODS:

A 58 year old male with severe COPD, previous hospitalizations due to COPD exacerbations, functional limitations due to shortness of breath, and motivation to improve his physical status was entered into the direct-to-home exercise project. He attended nine, one-hour visits with a physiotherapist consisting of a physician supervised exercise stress test, physical assessment, exercise set-up, bi-weekly follow-up appointments, and final evaluation after twelve weeks of exercise. Exercise prescriptions were individualized based on patient functional goals, clinical assessment findings, and practice guidelines. Pre and post-program outcome measures included Incremental Shuttle Walk Test (ISWT), Chronic Respiratory Questionnaire – Self Administered Individualized Format (CRQ-SAI), Modified Medical Research Council Dyspnea Scale (MMRC), Berg Balance Scale (BBS), Body Mass Index (BMI), and Waist to Hip Ratio (WHR).

RESULTS:

Significant improvements in functional aerobic capacity (+ 240m ISWT with a 38% increase in predicted peak oxygen uptake) and health related quality of life, particularly related to dyspnea ratings with functional activities (+2/7 CRQ-SAI and −2/5 MMRC) were observed. No significant changes were seen in BBS (+2/56), BMI (−1), or WHR (−0.03).

CONCLUSION:

Direct-to-home exercise programming in pulmonary rehabilitation may present a safe, effective, and feasible alternative for patients with COPD who are motivated to improve their functional status.

Footnotes

Financial support: No funding

Can Respir J. 2012 May-Jun;19(3):e44.

37: How Should We Measure Arm Exercise Capacity in COPD? A Systematic Review

Tania Janaudis-Ferreira 1,2, Marla K Beauchamp 1, Roger S Goldstein 1,2,3, Dina Brooks 1,2

Abstract

BACKGROUND

There are no recommendations on how to measure arm exercise capacity in individuals with chronic obstructive pulmonary disease (COPD). The objectives of this study were to: (i) synthesize the literature on measures of arm exercise capacity in individuals with COPD; (ii) describe the psychometric properties and the target construct of each measure and (iii) make recommendations for clinical practice and research.

METHODS:

Studies conducted in COPD that included a measure of arm exercise capacity were identified after searches of 5 electronic databases (MEDLINE, CINAHL, EMBASE, Physiotherapy Evidence Database and Cochrane Library) and reference lists of pertinent articles. One reviewer performed data extraction and two assessed quality of studies that described measurement properties using the Consensus-based standards for the selection of health measurement instrument.

RESULTS:

Of 654 reports, 41 met the study criteria. Five types of arm exercise tests were indentified: arm ergometry, ring shifts, dowel lifts, proprioceptive neuromuscular facilitation, and activities of daily living (ADL) tests. Four studies assessed measurement properties of the Unsupported Upper Limb Exercise test (UULEX), 6-minute Pegboard and Ring test (6PBRT), a test involving weight shifts and the Grocery Shelving Task (GST). Validity studies were of fair to good quality, whereas reliability studies were of poor quality.

CONCLUSIONS:

Arm ergometry may be best for measuring peak supported arm exercise capacity and endurance, while the UULEX, 6PBRT and GST may better reflect ADL and should be the tests of choice to measure peak unsupported arm exercise capacity (UULEX) and arm function (6PBRT and GST).

Can Respir J. 2012 May-Jun;19(3):e45.

38: Skeletal Muscle Atrophy is Associated with Physical Function in People with COPD

Priscila Robles 1,2, Dina Brooks 1,2, Roger Goldstein 1,3, Ali Naraghi 1,4, Marshall Sussman 1,4, Larry White 1,4, Sunita Mathur 1,2

Abstract

RATIONALE

Skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) includes the loss of muscle mass and muscle strength, which may account for impaired mobility and lower physical activity levels.

OBJECTIVE:

To compare skeletal muscle size in people with COPD to healthy controls using magnetic resonance imaging (MRI) and to correlate it with measures of muscle function and physical activity.

METHODS:

Seven individuals with moderate to severe COPD and seven control subjects underwent T1-weighted MRI to obtain maximal muscle cross-sectional area (CSAmax) of the quadriceps, hamstrings, dorsi- and plantar-flexors. Isometric and isokinetic peak torque of the same muscle groups, six-minute walk distance (6MWD) and physical activity levels using a questionnaire (PASE score) were also assessed.

RESULTS:

People with COPD and controls were matched for age (72±6.7 vs 69±9.3 yrs), sex (3 males, 4 females) and body mass index (25±6.2 vs 25±4.6 kg/m2). Compared with controls, people with COPD had 30% and 25% lower CSAmax of the quadriceps hamstrings and plantar-flexors respectively (p=0.01and p=0.03) whereas muscle strength was 60% lower in people with COPD for both muscle groups (p=0.009). 6MWD was lower in people with COPD (248 m vs 639 m; p=0.02); however, no difference was observed between groups for PASE score. Correlations were observed between CSAmax of the quadriceps and plantarflexors with peak torque (r=0.87 and r=0.83; p=0.001), 6MWD (r=0.79 and r=0.79; p=0.02) and PASE scores (r=0.58 and r=0.53; p=0.04).

CONCLUSION:

Muscle atrophy was observed across thigh and calf muscles of individuals with COPD and was associated with muscle strength, 6MWD and physical activity. Functional impairments in muscle strength were more profound than muscle atrophy and may be associated with poor muscle quality in people with COPD.

Can Respir J. 2012 May-Jun;19(3):e45.

39: Physical Activity Profile in Lung Transplant Candidates with Interstitial Lung Disease Undergoing Pulmonary Rehabilitation

Lisa Wickerson 1,2, Sunita Mathur 2, Polyana Mendes 2, Denise Helm 1, Lianne G Singer 1,3, Dina Brooks 2

Abstract

RATIONALE

Individuals with advanced interstitial lung disease (ILD) present with significant limitations in exercise capacity; however little is known about their levels of physical activity (PA). Pulmonary rehabilitation is recommended for lung transplant candidates, but its impact on daily activity has not been described. The objectives of this study were 1) to measure levels of daily PA in lung transplant candidates with ILD 2) compare levels of PA on rehabilitation days and on non-rehabilitation days and 3) explore the relationship between PA and muscle strength, functional exercise capacity and health-related quality of life (HRQOL).

METHODS:

A prospective cross-sectional sample of 24 lung transplant candidates with ILD underwent measurements of daily PA, quadriceps force (QF), functional exercise capacity (6-minute walk test (6MWT)) and HRQOL (Medical Short Form (SF-36) and St. George Respiratory Questionnaire (SGRQ)).

RESULTS:

Lung transplant candidates with ILD were inactive taking 2736±1612 daily steps and spending 6.8±10 minutes in moderate intensity PA per day. Participants took significantly higher steps (3784 vs. 2103 steps, p<0.001) and spent more time per day in moderate intensity PA (11.8 vs. 4.2 minutes, p<0.001) on rehabilitation verses non-rehabilitation days. There was a moderate correlation between daily steps and the 6MWT (r=0.57, p=0.004) and QF (r=0.5, p=0.02), as well as a moderate correlation between moderate intensity PA and the 6MWT (r=0.56, p=0.005). Conclusions: Lung transplant candidates with ILD have very low levels of PA corresponding to a third of the values of the general population. They can participate in a rehabilitation program and structured exercise increases their daily PA.

Footnotes

Financial support: ORCS and CRHP

Can Respir J. 2012 May-Jun;19(3):e45.

40: Energy Economy of Walking with a Wheeled Ambulatory Aid (Rollator) in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Kylie Hill 1,2,3,4, Thomas E Dolmage 1,5, Lynda Woon 1, Dina Brooks 1,2, Roger S Goldstein 1,2

Abstract

RATIONALE

Probst et al. (Chest 126: 1102, 2004) reported that, when using a rollator, patients with COPD increased their distance walked in 6 min along with increased oxygen uptake and ventilation. It was difficult to appraise economy (mechanical work to total energy expenditure) because the main determinant of the energy demand, speed, varied between conditions; hence, the authors concluded that rollator use improved distance by increasing ventilatory capacity and/or economy.

OBJECTIVE:

To determine whether walking with a rollator improved the energy economy in patients with COPD. The hypothesis was that oxygen uptake, at the same speed, would be lower (improved economy) when walking with a rollator.

METHODS:

Subjects completed 2 walks, (with and without a rollator) at individually set and constant speeds. At least 24 h later they repeated the session for a total of 4 walks. Energy expenditure was estimated from measured oxygen uptake using a telemetric system. Since mechanical work was kept constant (speed) during each walk, differences in economy were reflected in differences in energy expenditure in metabolic equivalents (METS).

RESULTS:

Ten subjects completed the study. Attainment of a steady state was confirmed during every walk. There was no effect of day (p=0.23) on energy expenditure. There was no significant difference (0.0 [−0.4 to 0.3] METs) in energy expenditure with (3.6 [2.9 to 4.3] METS) or without (3.6 [2.9 to 4.3] METS) the rollator.

CONCLUSION:

Rollator use does not acutely affect walking economy in patients with COPD. A better understanding of how people with COPD benefit from rollator use may facilitate their design and prescription.

SUPPORT:

Dr Brooks is supported by a Canada Research Chair and Dr Goldstein by the NSA Chair in Respiratory Rehabilitation Research

Can Respir J. 2012 May-Jun;19(3):e46.

41: Inflammatory Responses are Qualitatively, but not Quantitatively, Similar Between Airway and Monocyte-Derived Macrophages

Turki Alahmadi 1, Nurlan Dauletbaev 2, Kassey Herscovitch 2, Moishe Liberman 3, Larry C Lands 1

Abstract

RATIONALE

Airway macrophages (AM) are key airway innate immunity cells. Their inflammatory responses are often studied to gain insights into dysregulated airway inflammation. Retrieval of AM requires bronchoalveolar lavage (BAL), an invasive procedure. Macrophages can also be derived through in vitro maturation of peripheral blood monocytes; however, the similarities of inflammatory responses between these macrophages types are unclear. We asked whether monocyte-derived macrophages (MDM) would exhibit inflammatory responses qualitatively and quantitatively similar to AM.

METHOD:

To address this, we sampled AM (n=7) by BAL from intact lungs of patients undergoing cancer staging. AM were allowed to rest for 24 hours prior to stimulation. Blood monocytes (healthy volunteers; n=5) were isolated using Ficoll, purified by adherence to plastic, and cultured for 2 weeks in the presence of Macrophage Colony-Stimulating Factor to promote maturation. Both cell types were then stimulated for 1 hour with Lipopolysaccharide (LPS) or Interleukin (IL)-1β. Inflammatory responses in both macrophage types were gauged by production of IL-8 (ELISA) 4 hours after stimulation.

RESULTS:

In both AM and MDM, both LPS and IL-1β up-regulated IL-8. However, in both macrophage types, LPS was far more potent in stimulating IL-8, compared with IL-1β (p<0.05; all comparisons). We further observed that, while the pattern of IL-8 response was similar between AM and MDM, AM demonstrated weaker IL-8 responses to both LPS (∼7 fold increase in IL-8 vs. ∼40 fold in MDM) and IL-1β (∼1.3 fold increase vs. ∼15 fold in MDM).

CONCLUSION:

AM and MDM exhibit similar patterns of inflammatory responses. However, these responses are weaker in AM, possibly indicating their senescence or desensitization. MDM may cautiously be used as surrogates for AM in studies focusing on patterns of inflammatory responses.

Footnotes

Financial support: This work was funded by the Cystic Fibrosis Foundation

Can Respir J. 2012 May-Jun;19(3):e46.

42: Utilizing Near Infrared Spectroscopy and Indocyanine Green Dye to Estimate Respiratory and Leg Blood Flow During Continuous Exercise

Paolo B Dominelli 1, William R Henderson 1,2, Jordan A Guenettea, Donald EG Griesdale 2,3, Jordan S Querido 1, Robert Boushel 4, A William Sheel 1

Abstract

RATIONALE

Measurement of regional blood flow to the respiratory muscles has traditionally been invasive and impractical in exercise settings. The blood flow index (BFI), a minimally invasive method using indocyanine green dye and near infrared spectroscopy (NIRS), allows assessment of within subject changes in regional blood flow and can be performed during dynamic exercise. This study assessed the regional BFI to the vastus lateralis muscle and the superficial respiratory muscles in the seventh intercostal space during exercise.

METHODS:

Seven healthy subjects (28±6 yrs) cycled continuously at incrementally more difficulty stages to exhaustion. To determine the BFI, a bolus venous injection of ICG was performed during the final minute of each workload and the dye concentration was detected by emitting and receiving optodes secured to the skin. Ensemble averaged trans-pulmonary pressure-volume loops were integrated to determine the mechanical work of breathing (WOB). Data presented are means ± SE.

RESULTS:

At maximal exercise intensity, oxygen uptake was 56±6 ml•kg-1•min-1, ventilation was 120±8 l•min-1 and the WOB was 323±35 J•min-1. Respiratory muscle blood flow index (RMBFI) increased linearly until ∼65% of maximum work, whereafter it plateaued and declined. RMBFI was statistically lower at maximal exercise than at the two highest submaximal stages (p=0.04 and p<0.001, respectively) despite an increased WOB. The BFI to vastus lateralis displayed a similar pattern and was statistically lower at maximal exercise than at the two highest submaximal stages (p=0.04 and p<0.001, respectively).

CONCLUSION:

These findings suggest that there is competition between the respiratory and locomotor muscles for blood flow during sub-maximal and maximal exertion in healthy humans.

Can Respir J. 2012 May-Jun;19(3):e46.

43: Understanding the Role of Reactive Oxygen Species in Alveolar Formation of Neonatal Rat Lungs

Jamal Mobin 1,3, A Keith Tanswell 1,2,3

Abstract

RATIONALE

Reactive oxygen species (ROS), including lipid hydroperoxides (LOOH) and superoxide (O2•−), play a critical role as second messengers in many physiological processes, including lung cell DNA synthesis in response to growth factors. Unpublished studies in our laboratory have demonstrated that ROS can both stimulate (at low concentrations) and inhibit (at high concentrations) DNA synthesis by primary cultures of fetal lung cells. In this study we speculated that the increase in arterial partial pressure of oxygen at birth (from approximately 20 to 70 mmHg in the human) may induce low-level LOOH formation, which triggers postnatal alveolar formation from secondary crests in the neonatal rat.

METHODS:

Air-exposed neonatal rats were either uninjected or received daily subcutaneous injections of DPPD, a LOOH-scavenger, in corn oil or corn oil alone from days 1–6 of life. The effects of DPPD on lung growth were assessed by DNA synthesis, and by lung morphometry. Immunohistochemistry and Western blot were used to assess the effect of DPPD on growth factors known to mediate alveologenesis. DNA synthesis was also assessed for kidney sections.

RESULTS:

Treatment with DPPD resulted in a significant increase in tissue fraction, a significant reduction in both secondary crests/mm2 and secondary crests/tissue ratio, and a significant reduction in BrdU-positive cells/mm2, BrdU-positive secondary crests/mm2 and BrdU-positive secondary crests/tissue ratio. However, treatment with DPPD did not cause a significant change in lung volume. Parenchymal thickening was associated with decreased numbers of apoptotic cells and decreased expression of the proapoptotic cleaved caspases-3 and -7. DPPD did not cause a change in DNA synthesis of kidneys.

CONCLUSIONS:

LOOH play a critical role in postnatal alveolar formation in neonatal rats and exposure to DPPD results in an inhibition of physiological apoptosis, which contributes to the parenchymal thickening observed in the resultant lung injury.

Footnotes

Financial support: CIHR

Can Respir J. 2012 May-Jun;19(3):e47.

43A: IL-17A Positive Cells in the Lungs of Patients with Hypersensitivity Pneumonitis

Simon Hasan 1,2, Carol Gwozd 1,2, Abrar Alansary 1,2, Kerri Johannson 2, Margaret Mary Kelly 1,2,4

Abstract

RATIONALE

Hypersensitivity pneumonitis (HP) is an interstitial lung disease resulting from the repeated inhalation of a variety of aerosolized antigens. A marked pulmonary inflammatory response results, with increased numbers of lymphocytes, macrophages, mast cells and neutrophils present. A pro-inflammatory cytokine, interleukin(IL)-17A, has recently been shown to be central to the development of HP in an experimental animal model, but it is unknown if it is produced in the lung in the human disease. The commonest cells producing IL-17A in several other pulmonary inflammatory disorders have been reported to be lymphocytes.

OBJECTIVES:

To determine whether IL-17A is produced in the lung in HP and if so, which cells are responsible.

METHODS:

Human lung biopsies with a confirmed diagnosis of HP (n=8) as well as healthy control lungs (n=4) were obtained. Initially IL-17A immunohistochemistry was performed and positive cells were identified. Subsequently, double immunofluorescence was performed to determine which cell type was producing IL-17A, using tryptase (mast cells), CD3 lymphocytes), CD68 (macrophages) and myeloperoxidase (neutrophils).

RESULTS:

We found numerous cells staining strongly for IL-17A in the lungs from patients with HP, in contrast to very few in the control lungs. The majority of cells producing IL-17A were mast cells followed by neutrophils. These were the same cell types positive for IL-17A in the control lungs, although in much fewer numbers. We found scanty macrophages weakly positive for IL-17A in the HP group, with < 1% of IL-17A positive cells consisting of lymphocytes.

CONCLUSIONS:

This is the first report, to our knowledge, describing the presence of IL-17A positive cells in the lungs of patients with HP. The major cell types were mast cells and neutrophils, with a minute contribution from lymphocytes. The role of these IL-17A positive cells in HP needs to be explored further.

Footnotes

Financial support: Funded by Alberta Innovates & the Alberta Lung Association. Simon Hasan received a Calgary Laboratory Services Summer Studentship and a Markin USRP Scholarship

Can Respir J. 2012 May-Jun;19(3):e47.

44: A Preliminary Assessment of the Fungal Microbiome in the Lung

M Sze 1, PA Dimitriu 2, JV Gosselink 1, WM Elliott 1, MM Moore 3, S Adam 4, J Friedman 4, Y Zhao 5, R Varhol 5, D Miller 5, A He 5, R Moore 5, I Birol 5, WW Mohn 2, DD Sin 1, S Hayashi 1, JC Hogg 1

Abstract

BACKGROUND

Several studies have shown that a bacterial microbiome exists below the larynx; however, whether or not fungi reside within the lung microbiome has not been established. In severe COPD, airways are infiltrated with inflammatory immune cells that form tertiary lymphoid organs consistent with adaptive immune responses (NEJM 350:2645-53,2004). To determine whether fungi provide a source of persistent antigens that drive this adaptive immune response in severe COPD, a pilot study using unbiased massively parallel sequencing and quantitative PCR was used to detect fungal DNA.

METHODS:

DNA from peripheral lung tissue from a healthy smoker control (2 samples) and a COPD GOLD 4 patient (5 samples) was analyzed using the 75 based, pair-end tag sequencing (Illumina). Numbers of fungal genomes relative to human genomes were calculated from the respective numbers of reads. Following sequencing, non-smoker (n=8), smoker (n=8), COPD GOLD 4 (n=8), and cystic fibrosis (n=8) lung tissue was quantified for fungal specific ribosomal internal transcribed spacer 1 to 2 DNA by qPCR using A. fumigatus as a reference for the standard curve. Sterile water was used as the negative control.

RESULTS:

Sequence analysis showed an average of 39.7 fungi/1000 human cells was found in the samples from the COPD GOLD 4 individual and 38.9 in those from the smoking individual. Compared to the bacteria in these same samples (Am J Respir Crit Care Med 183; 2011:A1017) the fungi were higher (P < 0.05). qPCR confirmed the presence of fungi in the larger sample group. All sample groups were significantly higher than the negative non-template control (P<0.05).

CONCLUSION:

These preliminary results support the presence of small amounts of fungal DNA within the human lung microbiome and it is possible that foreign antigens derived from this source could provide antigens capable of driving an adaptive immune response in severe COPD.

Footnotes

Supported by: NIH # 5P50HL084922, 5P50HL084948, 1R01HL95388 and CIHR # CIF-97687

Can Respir J. 2012 May-Jun;19(3):e47.

45: The Lung Tissue Microbiome in COPD

M Sze 1, PA Dimitriu 2, JV Gosselink 1, WM Elliott 1, WW Mohn 2, DD Sin 1, S Hayashi 1, JC Hogg 1

Abstract

RATIONALE

In severe COPD airways are infiltrated with inflammatory immune cells that form tertiary lymphoid organs consistent with an adaptive immune response (NEJM 350:2645–53, 2004). Hilty et al. (PLoS One 5(1):e8578, 2010) demonstrated that human lungs contain a diverse microbiome. To determine whether bacteria within the lung microbiome might provide a source of antigens to drive the adaptive immune response in severe COPD, we utilized qPCR to quantify the abundance of bacteria, and terminal-restriction fragment length polymorphism (TRFLP) and 454 pyrotag sequencing to determine community composition.

METHODS:

DNA was obtained from banked lung tissue from 8 non-smokers, 8 smokers, and 8 COPD GOLD 4 patients. Lung tissue from 8 cystic fibrosis (CF) patients served as positive controls and sterile water as negative controls. The DNA was analyzed by qPCR of the bacterial 16S rRNA gene and the number of bacterial genomes was normalized to the number of human cells based on the RPP40 gene. The 16S rRNA gene was also analyzed by TRFLP and 454 pyrotag sequencing. The pyrotag sequencing was analyzed using principle coordinate and indicator species analysis.

RESULTS:

The bacteria/1000 human for all groups were greater than the negative control (P<0.001). TRFLP analysis showed three distinct bacterial communities: one for the smokers and non-smokers, another for the CF patients, and the third for COPD GOLD 4 patients. The 454-based analysis confirmed these results and showed that negative controls formed their own group separate from the others. Indicator species analysis identified four OTUs that were associated with the COPD GOLD 4 group (P<0.05). These OTUs aligned with bacteria in the genus Lactobacillus or Burkholderia.

CONCLUSION:

These results confirm the presence of a microbiome in human lungs and suggest that changes within this microbiome could provide foreign antigens capable of driving an adaptive immune response in very severe COPD.

Footnotes

Supported by: NIH # 5P50HL084922, 5P50HL084948, 1R01HL95388 and CIHR # CIF-97687

Can Respir J. 2012 May-Jun;19(3):e47–e48.

46: Pneumacult™-Ali: An Improved Media for Mucociliary Differentiation of Primary Human Bronchial Epithelial Cells

Samuel J Wadsworth 1, Michael J Riedel 2, Andrea Eskandar Afshari 2, Sharon A Louis 2, Delbert R Dorscheid 1

Abstract

RATIONALE

The human airway epithelium is a complex mucociliated structure that can be recapitulated in vitro by growing primary human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) culture. Current ALI methods often result in poor mucociliary differentiation that does not mimic the in vivo human airway. We have developed a serum-free medium (PneumaCultTM-ALI) that provides consistent and improved differentiation of HBEC cultures.

METHODS:

HBECs from six normal donors were obtained from Lonza or the International Institute for the Advancement of Medicine. Initial HBEC expansion was performed in BEGM (Lonza). Cells at passage 3 were seeded onto porous tissue culture inserts in either BEGM-based medium or PneumaCult™-ALI. Cells were grown to confluency in submerged culture, and then cultured at ALI for 21 days. Trans-epithelial electrical resistance (TEER), morphological characteristics, and expression of key proteins were measured weekly post-ALI.

RESULTS:

ALI cultures grown in PneumaCult™-ALI demonstrated stable TEER values that were consistently higher than inserts alone. At day 21 post-ALI, cultures grown in PneumaCult™-ALI have a significantly increased proportion of ciliated (66% vs. 52%) and mucous-producing (30% vs. 20%) apical cells compared to BEGM-based media, and a significant decrease in non-differentiated apical cells (4% vs. 28%). Mean cilia length was significantly increased in PneumaCult™-ALI cultures (6μm vs. 3μm). E-Cadherin and ZO-1 were expressed on the plasma membrane at equal levels in both culture conditions while expression of Muc5AC and cilia basal body protein were significantly increased in PneumaCult™-ALI cultures. Furthermore, PneumaCult™-ALI cultures responded to IL-13 treatment with goblet cell hyperplasia as assessed by PAS staining and Western blot.

CONCLUSIONS:

PneumaCult™-ALI is a novel defined media that provides consistent and improved mucociliary differentiation of primary HBECs in ALI cultures, creating a physiologically relevant model system for in vitro human lung epithelial cell research.

Footnotes

Funding sources: The National Sanitarium Association, StemCell Technologies Inc.

Can Respir J. 2012 May-Jun;19(3):e48.

47: Impact of Rapid Investigation Clinic on Timeliness of Lung Cancer Diagnosis and Staging

N Ezer 1,2, J Dallaire 1, K Schwartzman 1,2, AV Gonzalez 1,2

Abstract

RATIONALE

Lung cancer guidelines recommend prompt investigation and initiation of therapy. Diagnostic assessment units have been shown to decrease time to diagnosis for certain solid tumors; few studies have quantified their impact in lung cancer patients.

METHODS:

We evaluated the impact of a Rapid Investigation Clinic (RIC) on the timeliness of lung cancer diagnosis and staging at the McGill University Health Centre (MUHC), from February 2010 to June 2011. Within the RIC, investigation is conducted by a respirologist and a nurse clinician. A protocol based on recent guidelines is recommended. Priority is given to invasive procedures that allow simultaneous diagnosis and staging. Patients are subsequently referred to a multidisciplinary lung cancer clinic for therapeutic decisions. Controls were patients with a confirmed diagnosis of lung cancer, investigated outside the RIC at the same institution.

RESULTS:

A total of 145 lung cancer patients were investigated at the RIC compared to 103 patients in the control group. The mean age of RIC patients was 67 years, and 69 years in controls. NSCLC was diagnosed in 128 RIC patients (30% stages I–II; 70% stages III–IV) and 95 control patients (40% stages I–II; 60% stages III–IV). SCLC was diagnosed in 17 RIC patients and 8 controls. The median delay from first contact with an MUHC physician for suspected lung cancer (t0) and tissue confirmation was 28 days (mean 38 days) in the RIC and 32 days (mean 56 days) in the non-RIC patients. The average number of invasive diagnostic and/or staging procedures was similar in the two groups. Median delay between t0 and first medical or surgical treatment for lung cancer was 73 days (mean 78 days) for the RIC and 78 days (mean 104 days) for the non-RIC patients.

CONCLUSION:

A Rapid Investigation Clinic improves delays of lung cancer diagnosis and staging.

Footnotes

Financial support: Direction Québécoise du Cancer and MGH Foundation

Can Respir J. 2012 May-Jun;19(3):e48.

48: Out of Breath: Advance Care Planning and End of Life Care Initiatives in Pulmonary Rehabilitation

Susan M Haskell 1

Abstract

RATIONALE

89% of patients with advanced lung disease desire information on advance directives. They also desire end of life discussions during periods of stable health. Yet, there are barriers between these patients and their doctors which lead to a lack of communication on these subjects. Consequently, outpatient clinics and Pulmonary Rehabilitation (PR) programs offer an ideal opportunity to address such needs. This poster will demonstrate Eastern Health’s initiatives in the area of advance care planning (ACP) and end of life care in PR with Chronic Obstructive Pulmonary Disease (COPD) clients and their families.

METHODS:

A variety of methods including the utilization of pastoral care personnel, customized education sessions, The COPD Toolkit, Professional Development Education, as well as awareness campaigns and tools have been employed to meet ACP and end of life care needs.

RESULTS:

Patient feedback was consistent with the suggestion that ACP may actually decrease anxiety and depression in patients with chronic disease as it addresses two great concerns – loss of control over their lives and fear of becoming a burden to their families. Over the past year, The COPD Toolkit’s modified Advance Care Planning/Living Will educational session ranked a score of 4 or higher (on a scale of 1–7, where 1 is not very useful and 7 is extremely useful) amongst 95% of respondents. Resources such as the National Advance Care Planning day and Speak Up Wallet cards have been successful in getting people talking.

CONCLUSIONS:

Entering into discussion with COPD patients and their families about end of life matters is a worthwhile learning process. Clients and families appreciate such frank discussion and practical advice. Possible future considerations for enhanced ACP education include Clinical Pastoral Education for our team, continued knowledge translation activities, and follow up services to clients and families (as resources allow).

Can Respir J. 2012 May-Jun;19(3):e48–e49.

49: Acute Exacerbation of Interstitial Lung Disease Associated with Connective Tissue Disease: Report of Two Cases and Review of the Literature

Rohin Malhotra 1, Rebecca Kruisselbrink 1, Gerard Cox 1

Abstract

The management of patients with acute exacerbations of interstitial lung disease is medically and ethically challenging. Professional guidelines to assist decision-making are not currently available.

We present two cases. The first was a 35-year old woman diagnosed with mixed connective tissue disease and biopsy-confirmed non-specific interstitial pneumonia. She developed respiratory failure requiring intubation two months after lung biopsy. Workup revealed no reversible trigger; despite aggressive treatment with steroids, cyclophosphamide, and eventually Rituximab, she succumbed to intractable hypoxia. A second patient was a 58-year old woman with rheumatoid arthritis. Six months of worsening dyspnea led to a diagnosis of usual interstitial pneumonia based on high-resolution CT scan. Although referred for transplant consideration early in her course, she developed hypoxic respiratory failure requiring non-invasive ventilation within months of diagnosis. Workup was negative; empiric antibiotics, anticoagulation, and steroids were administered, and she was transferred to the transplant center. She deteriorated shortly after transfer, was intubated, and died five days later.

Interstitial lung disease comprises a heterogeneous group of disorders sharing clinical, radiographic, and pathological features. Idiopathic pulmonary fibrosis has a median duration of three years; there is no proven successful treatment. Acute exacerbations are common; outcomes are poor, and mechanical ventilation is often futile. In contrast, connective tissue disease-associated ILD is believed to have a better prognosis and be more responsive to therapy. Our experience shows, however, that sudden, devastating exacerbations do occur in this group, and there is a marked paucity of published data regarding the best approaches to management and prognostication in this situation.

Through these case reports and literature review, we summarize current teaching on the clinical course and prognosis of CTD-associated ILD as compared to idiopathic pulmonary fibrosis, focusing on the acute, hypoxic exacerbation. We identify clinical features that may be prognostic indicators in acute exacerbations. Our goal is to assist physicians caring for acutely ill ILD patients through management recommendations for a devastating disease process guided by little published data, and fraught with difficult decision-making.

Can Respir J. 2012 May-Jun;19(3):e49.

50: Clinicopathological Conferences in the Canadian Respiratory Journal: A New Format for Maximizing the Educational Value of Case Reports

George Rakovich 1, Katherine Thain 2, Brian Vukusic 3, Peter D Paré 4

Abstract

BACKGROUND

There is a decreasing interest in publishing case reports, due to a perception that case reports are not a valid or reliable source of scientific information. On the other hand, case presentations are recognized as a useful form of CME and are used on a regular basis as a learning tool in residency education, usually in the form of multi-disciplinary clinico-pathological conferences. These are often high-quality presentations rich in educational content, which are seldom given an opportunity for publication.

The potential educational value of case reports has received little attention, and the few journals that continue to publish case reports do so without any clear learning objectives. Therefore, we believe that there is an opportunity to improve the educational content and value of case reports.

OBJECTIVES:

To develop and implement a new format for case reports in order to focus content and maximize educational value of cases published in the Canadian Respiratory Journal (CRJ).

METHODS:

We have described a new format for case reporting that relies on 1–2 focused learning objectives, a CanMEDS competency objective and a brief pre-post test which would allow readers to be automatically credited with CME points through CRJ’s online system.

In order to enhance educational content, we have also initiated a collaboration with Canadian chest medicine and thoracic surgery programs that will create a pathway for publishing cases presented by trainees at local clinico-pathological conferences.

CONCLUSION:

The new format will be evaluated by a formal online survey 1 year following its implementation. We are hopeful that it will increase the appeal and educational value of case reports published in CRJ, and it may represent a useful model for the future publication of case reports in biomedical journals.

Can Respir J. 2012 May-Jun;19(3):e49.

51: Non Invasive Ventilation on Acute and Chronic Care Units: Is it Safe?

Julie Dallaire 1, Sandra Dial 1, Franceen Browman 1, Lorine Jean-Marie 1, Odile Begin 1, Chantal Souligny 1, Constance Reid 1

Abstract

The goal is to present the clinical pathway for the management of patients with acute respiratory failure, chronic respiratory failure and palliative care with Non Invasive Ventilation (NIV) on acute and chronic care units. It is generally recognized that Non Invasive Ventilation (NIV), is mainly initiated and used in monitored settings such as in ICU. However, at the Montreal Chest Institute (MCI), McGill University Health Centre (MUHC), because of our expertise and specialization in respiratory care as well as increasing needs for ventilation assistance in our population, this mode of ventilation is used in non-ICU settings such as acute care wards. Concerns arose regarding the quality and safety of the care provided to these patients. For this reason an interdisciplinary committee was created to develop and to institute guidelines to maximize safe administration of NIV on the ward.

OBJECTIVES OF THE COMMITTEE:

1-To develop guidelines regarding use of NIV in the institution, 2-To determine optimal monitoring standards for care of the patient on NIV, 3- To tailor the treatment plan according to the patient’s needs as determined by the health care team, 4-To craft a NIV flow sheet to be used both by Nursing and Respiratory Therapy to facilitate the documentation of the patient’s condition and his/her management. 4- To prevent mistakes. 5- To communicate the guidelines to all members of the MCI health care team.

METHODS:

We have developed a 3hours training module; we advertised the implementation of the protocol with poster throughout the institution; we set up a NIV promotional booth.

RESULTS:

pre-implementation there was 137 patients have been transferred to the MCI with NIV. From those patients, 9 have been transferred to the ICU. In 2010, post-implementation, 70 patients have been transferred to the MCI with NIV and from those patients, 7 have been transferred to the ICU.

CONCLUSION:

With the implementation of the NIV protocol, the ICU attending is immediately consulted when a patient needs NIV (acute respiratory failure), and less patients were accepted in our institution when they were unstable (135 in 209 vs 70 in 2010).

Footnotes

Funding: No financial support.

Can Respir J. 2012 May-Jun;19(3):e49–e50.

52: Pediatric Sickle Cell Disease and Airway Hyperreactivity: Prevalence in Asymptomatic Patients

Natalie Shilo 1, Nancy Robitaille 2, Yves Pastore 2, Denis Bérubé 3, Sheila V Jacobs 3, Sharon Abish 4, Larry Lands 1

Abstract

RATIONALE

Asthma is a negative prognostic factor in sickle cell disease (SCD). Yet children with SCD are not routinely screened. Possibly, a significant number of children with SCD, who do not have a recent history of acute chest syndrome (ACS) or respiratory complaints, do have AHR, but remain undiagnosed. Potentially, the window for delaying the progression of lung disease is being missed. Methacholine challenge testing could examine whether the prevalence of AHR is under recognized in this sub-group of clinically asymptomatic patients, and if routine screening for asthma is thus indicated in this population.

METHODS:

Children with SS, SC, and Sβ0-thalassemia disease between the ages of 8–18 years are being enrolled. Subjects with asthma, or on bronchodilator, inhaled corticosteroid, or leukotriene antagonist therapy, are excluded. An ACS episode should not have occurred over the past year, necessitated a blood transfusion, or required a PICU admission. Subjects with a vaso-occlusive episode or respiratory infection within the past 30 days, or a blood transfusion within the past 90 days, are excluded.

All subjects perform a methacholine challenge. A methacholine challenge is positive if the FEV1 decreases by ≥20% in response to <4mg/ml methacholine.

RESULTS:

To date, three patients have been enrolled. All had a positive methacholine challenge test.

CONCLUSIONS:

The goal is for a total of 50 patients to be enrolled. Our preliminary results suggest that AHR is under recognized in children with SCD who have not had a recent history of respiratory complaints.

Footnotes

Financial Support: The Montreal Children’s Hospital, McGill University Health Centre, Department of Pediatric Respiratory Medicine, Internal funds

Can Respir J. 2012 May-Jun;19(3):e50.

53: The Canadian Respiratory Journal Comes of Age (18) and Goes Online!

Katherine R Thain 1, Peter Pare 1

Abstract

BACKGROUND

The Canadian Respiratory Journal (CRJ) was begun in 1994 and until 2001 was edited by Dr Norman Jones from McMaster. Between 2001 and 2011 the editor in chief was Nick Anthonisen from Winnipeg. Under their leadership the CRJ grew in stature and has become an important means of communication and education for the medical community in Canada and internationally. Until the beginning of May 2011, all submissions were in hard-copy paper form. Beginning in May of 2011, at the age of 18 years, the CRJ went to an online only submission system.

OBJECTIVES:

To compare differences in demographics and statistics of submissions after the changeover from paper-only to online-only submissions

METHODS:

We have performed descriptive statistics to examine the differences in the types of manuscripts that were submitted during the paper-only era and have been submitted since the start of the current online-only submission processes. In addition, we have compared various parameters such as the differences in time-to-publish between the two processes as well as the time from submission to review, from submission to acceptance and the statistical differences between Canadian and International submissions.

RESULTS:

There are significant differences in article types, number of submissions and countries of origin between the two submission formats. For example, 70% of paper-only submissions were received from within Canada but since transition to online-only submissions this has completely reversed with 70% of submissions being received from international sources.

CONCLUSION:

Many differences exist between a paper-only and an online-only submission system. It remains to be seen how these difference will affect the impact factor of the Journal.

Articles from Canadian Respiratory Journal : Journal of the Canadian Thoracic Society are provided here courtesy of Wiley

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