Robert D Levy

Vancouver General Hospital, Vancouver, British Columbia, Canada

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Publications (43)129.26 Total impact

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    ABSTRACT: Prior to the availability of the pulmonary arterial hypertension (PAH)-specific therapy, PAH was a dreadful disease with a very poor prognosis. Better understanding of the complex pathobiology of PAH has led to a major therapeutic evolution. International regulatory agencies have approved many specific drugs with different pharmacologic pathways and routes of administration. In the year 2013, two new drugs with great potentials in managing PAH have been added to the treatment options, macitentan and riociguat. Additional drugs are expected to come in the near future. A substantial body of evidence has confirmed the effectiveness of pulmonary arterial hypertension (PAH)-specific therapies in improving the patients' symptomatic status and slowing down the rate of clinical deterioration. Although the newer modern medications have significantly improved the survival of patients with PAH, it remains a non-curable and fatal disease. Lung transplantation (LT) remains the only therapeutic option for selected patients with advanced disease who continue to deteriorate despite optimal therapy.
    Annals of Thoracic Medicine 07/2014; 9(Suppl 1):S79-91. · 1.12 Impact Factor
  • Majdy M Idrees, John Swiston, Robert D Levy
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    ABSTRACT: Treatment of pulmonary hypertension (PH) patients is challenging and should only be initiated after a comprehensive diagnostic evaluation. Such treatment should ideally be done in specialized centers with full capability for hemodynamic measurements, having access to a broad range of PAH therapies, and adequate experience in the management of critically ill patients. The following discussion is intended to review the general measures and the non-specific (supportive) therapy used in managing PH patients, while the specific therapy will be discussed in a subsequent different article.
    Annals of Thoracic Medicine 07/2014; 9(Suppl 1):S74-8. · 1.12 Impact Factor
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    ABSTRACT: The Saudi Association for Pulmonary Hypertension (previously called Saudi Advisory Group for Pulmonary Hypertension) has published the first Saudi Guidelines on Diagnosis and Treatment of Pulmonary Arterial Hypertension back in 2008.[1] That guideline was very detailed and extensive and reviewed most aspects of pulmonary hypertension (PH). One of the disadvantages of such detailed guidelines is the difficulty that some of the readers who just want to get a quick guidance or looking for a specific piece of information might face. All efforts were made to develop this guideline in an easy-to-read form, making it very handy and helpful to clinicians dealing with PH patients to select the best management strategies for the typical patient suffering from a specific condition. This Guideline was designed to provide recommendations for problems frequently encountered by practicing clinicians involved in management of PH. This publication targets mainly adult and pediatric PH-treating physicians, but can also be used by other physicians interested in PH.
    Annals of Thoracic Medicine 07/2014; 9(Suppl 1):S1-S15. · 1.12 Impact Factor
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    ABSTRACT: We sought to determine and compare the prevalence of nonadherence in lung, kidney, and liver transplant recipients, and identify potential risk factors for nonadherence. This cross-sectional, single-center, retrospective cohort study, evaluated 225 outpatient lung, kidney, and liver transplant recipients' adherence to immunosuppressant medication. Based on immunosuppressant dosages and dispensing records, medication possession ratio (days of medication supplied/actual days) and gaps in prescription refills (> 30-day lapse between expected depletion of supply and next refill) were used as surrogate markers in assessing adherence for 2 years. Patients were adherent to their immunosuppressant medication regimens if their medication possession ratio was ≥ 80%. The mean age of the subjects was slightly greater than 50 years of age, and they were a median of 2.0, 1.3, and 1.1 years posttransplant at the start of data collection for lung, kidney, and liver recipients. Overall medication possession ratios were 95.4% ± 7.5%, 95.9% ± 7.6%, and 92.7% ± 12.3% in our lung, kidney, and liver recipients. Only 7.1% of patients had a medication possession ratio lower than 80%, which was the cutoff for nonadherence. No statistical analyses were performed to identify potential factors for nonadherence because of the small number of nonadherent patients. Immunosuppressant medication adherence at our center was high for all 3 organ cohorts, as measured by a medication possession ratio of 80% or better. Further study is needed to evaluate immunosuppressant adherence over time after transplant, and confirm the clinical factors that optimize adherence in high-risk patients.
    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 12/2013; 11(6):475-481.
  • Philip Hui, Blair Walker, Robert D Levy
    Chest 11/2012; 142(5):1348-51. · 7.13 Impact Factor
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    ABSTRACT: Endothelin receptor antagonists are commonly used in the treatment of pulmonary hypertension. Sitaxsentan, a selective endothelin A receptor blocker, induces a mild transaminitis in approximately 3% to 5% of patients, but rarely an acute severe hepatitis. A case involving a 61-year-old female with sitaxsentan-induced acute severe liver failure is presented. Depite withdrawal of therapy, her liver tests failed to improve. After six weeks of monitoring, the patient was administered high-dose corticosteroids, with a good clinical and biochemical response. While endothelin receptor antagonists are postulated to cause hepatitis by inhibition of a bile salt transporter pump, an immune-mediated or idiosyncratic mechanism should be considered.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2012; 19(1):e1-2. · 1.29 Impact Factor
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    ABSTRACT: Acute exacerbations of interstitial lung disease present as clinical deteriorations, with progressive hypoxemia and parenchymal consolidation not related to infection, heart failure or thromboembolic disease. Following single lung transplantation, patients receive maintenance immunosuppression, which could mitigate the development of acute exacerbations in the native lung. A 66-year-old man with fibrotic, nonspecific interstitial pneumonitis presented with fever, hypoxemia and parenchymal consolidation limited to the native lung four years after single lung transplantation. Investigations were negative for infection, heart failure and thromboembolic disease. The patient worsened over the course of one week despite broad-spectrum antimicrobial therapy, but subsequently improved promptly with augmentation of prednisone dosed to 50 mg daily and addition of N-acetylcysteine. Hence, the patient fulfilled the criteria for a diagnosis of an acute exacerbation of pulmonary fibrosis in his native lung. Clinicians should consider acute exacerbation of parenchymal lung disease of the native lung in the differential diagnosis of progressive respiratory deterioration following single lung transplantation for pulmonary fibrosis.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2012; 19(1):e3-4. · 1.29 Impact Factor
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    ABSTRACT: Many treatment options are now available for patients with idiopathic pulmonary arterial hypertension (IPAH). Data regarding the optimal combination of therapies are lacking, as is consensus on how to assess response to therapy and when to change therapeutic regimens. To gather the opinions of Canadian pulmonary hypertension (PH) experts regarding standard practice in the care of IPAH patients after therapy is initiated. Canadian PH physicians were surveyed using short questionnaires to assess their opinions and practices in the care of IPAH patients. A Delphi forecasting approach was used to gain consensus among Canadian physicians on the most important clinical parameters to consider when assessing patients after the initiation of therapy. Twenty-six of 37 Canadian PH experts who were invited to participate completed the study. All endorsed the use of combination therapy for IPAH patients despite the lack of universal provincial coverage for this approach. By consensus, WHO functional class, 6 min walk distance and hospitalization for right heart failure were the most important clinical parameters. The most highly rated physical examination parameters were jugular venous pressure, peripheral edema, the presence of ascites and body weight. The overall approach to care of IPAH patients is similar across PH centres in Canada. A limited number of clinical and physical examination parameters were considered to be most important to reassess patients after therapy is initiated. These parameters, along with definition of threshold values, will facilitate the development of standard practice guidelines for IPAH patients in Canada.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 07/2011; 18(4):230-4. · 1.29 Impact Factor
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    ABSTRACT: There have been very few reports describing postlung transplant outcomes in patients' infected⁄colonized with Burkholderia gladioli pretransplant. A case involving a lung transplant recipient with cystic fibrosis who ultimately died as a result of severe rhinosinusitis due to B gladioli infection in the context of postlung transplant immunosuppression is reported.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 07/2011; 18(4):e64-5. · 1.29 Impact Factor
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    ABSTRACT: The present report describes two patients with long-term survival after being diagnosed with idiopathic pulmonary arterial hypertension more than 20 years earlier. Both patients were treated with calcium channel blockers for several years and are currently maintained on bosentan, an oral endothelin receptor antagonist. Severe dilation of the main pulmonary arteries is present in both patients and may be related to long-term survival with idiopathic pulmonary arterial hypertension.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2011; 18(3):e50-1. · 1.29 Impact Factor
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    ABSTRACT: Severe α₁-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α₁-antitrypsin, but whether they have an increased risk of COPD is uncertain. We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. PI MZ was associated with a 3.5% lower FEV₁/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV₁/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Compared with PI MM individuals, PI MZ heterozygotes had lower FEV₁/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals.
    Chest 11/2010; 138(5):1125-32. · 7.13 Impact Factor
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    ABSTRACT: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q. We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q. Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families in the Boston Early-Onset COPD Study. Merging the results of the two case-control analyses, 14 of the 790 overlapping SNPs had a combined P < 0.01. Two of these 14 SNPs were consistently associated with COPD in the ICGN families. The association with one SNP, located in the gene XRCC5, was replicated in the Boston Early-Onset COPD Study, with a combined P = 2.51 x 10(-5) across the four studies, which remains significant when adjusted for multiple testing (P = 0.02). Genotype imputation confirmed the association with SNPs in XRCC5. By combining data from COPD genetic association studies conducted in four independent patient samples, we have identified XRCC5, an ATP-dependent DNA helicase, as a potential COPD susceptibility gene.
    American Journal of Respiratory and Critical Care Medicine 05/2010; 182(5):605-13. · 11.04 Impact Factor
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    ABSTRACT: Pulmonary embolism is a common condition. Some patients subsequently develop chronic thromboembolic pulmonary hypertension (CTEPH). Many care gaps exist in the diagnosis and management of CTEPH patients including lack of awareness, incomplete diagnostic assessment, and inconsistent use of surgical and medical therapies. A representative interdisciplinary panel of medical experts undertook a formal clinical practice guideline development process. A total of 20 key clinical issues were defined according to the patient population, intervention, comparator, outcome (PICO) approach. The panel performed an evidence-based, systematic, literature review, assessed and graded the relevant evidence, and made 26 recommendations. Asymptomatic patients postpulmonary embolism should not be screened for CTEPH. In patients with pulmonary hypertension, the possibility of CTEPH should be routinely evaluated with initial ventilation/perfusion lung scanning, not computed tomography angiography. Pulmonary endarterectomy surgery is the treatment of choice in patients with surgically accessible CTEPH, and may also be effective in CTEPH patients with disease in more 'distal' pulmonary arteries. The anatomical extent of CTEPH for surgical pulmonary endarterectomy is best assessed by contrast pulmonary angiography, although positive computed tomography angiography may be acceptable. Novel medications indicated for the treatment of pulmonary hypertension may be effective for selected CTEPH patients. The present guideline requires formal dissemination to relevant target user groups, the development of tools for implementation into routine clinical practice and formal evaluation of the impact of the guideline on the quality of care of CTEPH patients. Moreover, the guideline will be updated periodically to reflect new evidence or clinical approaches.
    Canadian respiratory journal: journal of the Canadian Thoracic Society 01/2010; 17(6):301-34. · 1.29 Impact Factor
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    ABSTRACT: The benefits of exercise training in individuals with chronic lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease have been well documented. Although there is limited research available, it appears that exercise is safe and beneficial for people with severe end-stage chronic lung disease who are awaiting lung transplantation in addition to recipients of lung transplants. Evidence-based guidelines for exercise training in the pre- and post-lung transplantation phases have not yet been developed. However, by considering exercise guidelines for people with chronic lung disease and in older adults in light of the physiological changes that can occur either pre- or post-lung transplantation, a safe and appropriate exercise training program can be developed. Depending on the individual's exercise capacity and goals, the training program may include aerobic and resistance exercise, and flexibility and balance training. In the pre-transplant and acute post-transplant phases, the intensity of exercise is dictated primarily by symptom limitation and adequate rest, which is required between exercise bouts to allow for recovery. In the post-transplant phase, it is possible for lung transplant recipients to increase their exercise capacity and even participate in sports. Further research needs to be conducted to determine the optimal training guidelines and the long-term benefits of exercise, both in lung transplant candidates and recipients.
    The Physician and sportsmedicine 10/2009; 37(3):78-87. · 1.34 Impact Factor
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    ABSTRACT: The authors of previous reports have suggested that women are more susceptible to cigarette smoke and to an airway-predominant COPD phenotype rather than an emphysema-predominant COPD phenotype. The purpose of this study was to test for sex differences in COPD phenotypes by using high-resolution CT (HRCT) scanning in male and female smokers with and without COPD. All subjects completed spirometry and answered an epidemiologic respiratory questionnaire. Inspiratory HRCT scans were obtained on 688 smokers enrolled in a family-based study of COPD. Emphysema was assessed by using a density mask with a cutoff of -950 Hounsfield units to calculate the low-attenuation area percentage (LAA%) and by the fractal value D, which is the slope of a power law analysis defining the relationship between the number and size of the emphysematous lesions. Airway wall thickness was assessed by calculating the square root of the airway wall area (SQRTWA) and the percentage of the total airway area taken by the airway wall (WA%) relative to the internal perimeter. Women had a similar FEV(1) (women, 65.5% +/- 31.9% predicted; men, 62.1% +/- 30.4% predicted; p = 0.16) but fewer pack-years of cigarette smoking (women, 37.8 +/- 19.7 pack-years; men, 47.8 +/- 27.4 pack-years; p < 0.0001). Men had a greater LAA% (24% +/- 12% vs 20% +/- 11%, respectively; p < 0.0001) and larger emphysematous spaces than women, and these differences persisted after adjusting for covariates (weight, pack-years of smoking, current smoking status, center of enrollment, and FEV(1) percent predicted; p = 0.0006). Women had a smaller SQRTWA and WA% after adjusting for covariates (p < 0.0001). Male smokers have more emphysema than female smokers, but female smokers do not show increased wall thickness compared with men.
    Chest 08/2009; 136(6):1480-8. · 7.13 Impact Factor
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    ABSTRACT: Home-based rehabilitation is a promising approach to improve access to pulmonary rehabilitation. To assess whether self-monitored, home-based rehabilitation is as effective as outpatient, hospital-based rehabilitation in patients with chronic obstructive pulmonary disease (COPD). Randomized, multicenter, noninferiority trial. 10 academic and community medical centers in Canada. 252 patients with moderate to severe COPD. After a 4-week education program, patients took part in home-based rehabilitation or outpatient, hospital-based rehabilitation for 8 weeks. They were followed for 40 weeks to complete the 1-year study. The primary outcome was the change in Chronic Respiratory Questionnaire dyspnea subscale score at 1 year. The primary analysis took a modified intention-to-treat approach by using all patients who provided data at the specified follow-up time, regardless of their level of adherence. The analysis used regression modeling that adjusted for the effects of center, sex, and baseline level. All differences were computed as home intervention minus outpatient intervention. Both interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, -0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention. The contribution of the educational program to the improvement in health status and exercise tolerance cannot be ascertained. Home rehabilitation is a useful, equivalent alternative to outpatient rehabilitation in patients with COPD.
    Annals of internal medicine 01/2009; 149(12):869-78. · 13.98 Impact Factor
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    ABSTRACT: To compare the detection rate of pulmonary abnormalities between conventional high-resolution computed tomography (HRCT) and high-resolution multidetector computed tomography (MDCT) in lung transplant recipients and to correlate a composite computed tomography (CT) score with bronchiolitis obliterans syndrome (BOS) stage. Twenty-four lung transplant recipients (12 single/12 double lung transplants, 13 males/11 females, mean age: 53 y, range: 28 to 71) underwent contiguous 16-slice high-resolution MDCT of the lungs at maximal inspiration and maximal expiration. Eight reformatted image sets were reconstructed: (i) contiguous 1-mm slice MDCT image set in the transverse, sagittal, and coronal image planes at maximal inspiration; (ii) contiguous 1-mm slice MDCT image set in the transverse, sagittal, and coronal image planes at maximal expiration; (iii) conventional HRCT image set of 1-mm slices every 10 mm at maximal inspiration; and (iv) conventional expiratory HRCT of 1-mm slices at 3 selected levels at maximal expiration. Individual pulmonary abnormalities were added to give a composite CT score. Individual abnormalities and the composite CT score were correlated with BOS stage, as based on functional testing of airflow obstruction, for each of the 8 image sets. Transverse, sagittal, and coronal MDCT correlated significantly with BOS stage (R=0.46, 0.49, 0.52, respectively), whereas conventional HRCT did not. Multiple regression analysis demonstrated that transverse MDCT was the only independent predictor of BOS stage (R=0.33, P<0.01). Interobserver agreement for composite CT scores for HRCT, transverse, sagittal, and coronal MDCT were R2=0.89, 0.87, 0.83 and 0.80, respectively. Interobserver agreement for individual abnormalities was better with MDCT than with conventional HRCT. In lung transplant recipients, high-resolution MDCT detects significantly more pulmonary abnormalities and has better interobserver agreement than conventional HRCT and is an independent predictor of BOS stage.
    Journal of thoracic imaging 12/2008; 23(4):235-43. · 1.42 Impact Factor
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    ABSTRACT: Solid organ transplantations are among the most expensive treatments yet relatively few investigators have reported well-characterized and reliable information on costs. The objective here was to compare the direct medical costs of kidney, liver, heart, and lung transplantations in British Columbia (BC), Canada. Using data from a province-wide population-based registry, resource utilization data were collated for 1333 patients who underwent solid organ transplantation between 1995 and 2003. Resource categories included hospital stays, physician fees, laboratory and diagnostic testing, and immunosuppressants. Mean costs (2003 $CDN) were derived for the index hospitalization and each of the 2 years after hospital discharge. To enable valid comparisons, the same costing methodology was applied to all four programs. The mean costs of transplantation varied from $27,695 for kidney recipients to $89,942 for lung recipients, with inpatient hospital stays comprising the largest component. Mean costs for the first and second follow-up years ranged from $27,592 and $11,424 for lung recipients to $21,144 and $8086 for liver recipients. Immunosuppressants accounted for between two-thirds and three-fourths of costs by the second year. Within each program, variations in costs could not be accounted for by demographic factors. We observed in BC a threefold variation in mean costs of organ transplantation procedures, with the variations between programs diminishing during follow-up. Policymakers and decision-makers seeking to better understand the deployment of resources for transplantation may focus on clinical factors at the time of hospitalization and factors that influence use and costs of immunosuppressants during the induction and maintenance phases.
    Value in Health 10/2008; 12(2):282-92. · 2.19 Impact Factor
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    Sunita Mathur, Robert D Levy, W Darlene Reid
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    ABSTRACT: Purpose: Exercise limitation in recipients of lung transplant may be a result of abnormalities in the skeletal muscle. However, it is not clear whether these abnormalities are merely a reflection of the changes observed in the pretransplant condition. The purpose of this paper was to compare thigh muscle volume and composition, strength, and endurance in lung transplant recipients to people with chronic obstructive pulmonary disease (COPD).Methods: Single lung transplant recipients (n=6) and people with COPD (n=6), matched for age, sex, and BMI participated in the study. Subjects underwent MRI to determine muscle size and composition, lower extremity strength testing and an isometric endurance test of the quadriceps.Results: Lung transplant recipients had similar muscle volumes and intramuscular fat infiltration of their thigh muscles and similar strength of the quadriceps and hamstrings to people with COPD who had not undergone transplant. However, quadriceps endurance tended to be lower in transplant recipients compared to people with COPD (15 +/- 7 seconds in transplant versus 31 +/- 12 seconds in COPD, p = 0.08).Conclusions: Recipients of lung transplant showed similar changes in muscle size and strength as people with COPD, however muscle endurance tended to be lower in people with lung transplants. Impairments in muscle endurance may reflect the effects of immunosuppressant medications on skeletal muscle in people with lung transplant.
    Cardiopulmonary physical therapy journal. 09/2008; 19(3):84-93.
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    ABSTRACT: It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families. To determine whether airway wall thickening and emphysema (1) make independent contributions to the severity of COPD and (2) show independent aggregation in families of individuals with COPD. Index cases with COPD and their smoking siblings underwent spirometry and were offered high-resolution computed tomography scans of the thorax to assess the severity of airway wall thickening and emphysema. A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non-COPD-related thoracic disease. Airway wall thickness correlated with pack-years smoked (P < or = 0.001) and symptoms of chronic bronchitis (P < 0.001). FEV(1) (expressed as % predicted) was independently associated with airway wall thickness at a lumen perimeter of 10 mm (P = 0.0001) and 20 mm (P = 0.0013) and emphysema at -950 Hounsfield units (P < 0.0001). There was independent familial aggregation of both the emphysema (adjusted odds ratio, 2.1; 95% confidence interval, 1.1-4.0; P < or = 0.02) and airway disease phenotypes (P < 0.0001) of COPD. Airway wall thickening and emphysema make independent contributions to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes.
    American Journal of Respiratory and Critical Care Medicine 06/2008; 178(5):500-5. · 11.04 Impact Factor

Publication Stats

453 Citations
129.26 Total Impact Points

Institutions

  • 2014
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 2002–2014
    • University of British Columbia - Vancouver
      • • Division of Respiratory Medicine
      • • Department of Medicine
      • • Faculty of Pharmaceutical Sciences
      Vancouver, British Columbia, Canada
  • 2011
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
  • 2009
    • University of Toronto
      • Department of Physical Therapy
      Toronto, Ontario, Canada