[Show abstract][Hide abstract] ABSTRACT: Interstitial lung disease (ILD) classification requires a multidisciplinary review that includes input from an ILD clinician, chest radiologist, and lung pathologist. We report a case of ILD that remained unclassifiable due to discordant clinical, radiological, and pathological findings despite a thorough evaluation that included examination of explanted lung tissue. This case demonstrates that ILD can remain unclassifiable even with a complete evaluation and illustrates one approach to the management of such patients.
[Show abstract][Hide abstract] 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. DOI:10.4103/1817-1737.134043 · 1.80 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.4103/1817-1737.134041 · 1.80 Impact Factor
[Show abstract][Hide abstract] 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. 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. DOI:10.4103/1817-1737.134006 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulmonary arteritis is a rare cause of pulmonary hypertension. Causes of pulmonary arteritis can be divided into primary and secondary, as well as classified according to vessel size. Only large vessel vasculitis is associated with pulmonary hypertension; primary forms include Takayasu arteritis and giant cell arteritis. The diagnosis of pulmonary arteritis can be challenging and the associated morbidity is serious without prompt, directed treatment. The authors present a case involving a 48-year-old First Nations man presenting with a six-month history of exertional dyspnea and severe stenosis of the left pulmonary artery, who was ultimately diagnosed with pulmonary arteritis related to large vessel vasculitis.
Canadian respiratory journal: journal of the Canadian Thoracic Society 02/2014; 21(3). · 1.66 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. · 1.66 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.1164/ajrccm-conference.2011.183.1_MeetingAbstracts.A5671 · 1.66 Impact Factor
[Show abstract][Hide abstract] 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. · 1.66 Impact Factor
[Show abstract][Hide abstract] 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. · 1.66 Impact Factor
[Show abstract][Hide abstract] 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 05/2011; 18(3):e50-1. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intravenous epoprostenol, a prostaglandin analogue, has been a mainstay of therapy for patients with advanced pulmonary arterial hypertension (PAH) since the early 1990s. This medication has multiple side effects, and sudden discontinuation is potentially associated with severe sequelae. Several recent case series have described the transition from intravenous to newer oral or subcutaneous therapies. A case series detailing the authors' experience with such transitions, and a systematic lierature review is presented.
All consecutive PAH patients seen at the Vancouver Pulmonary Hypertension Clinic (Vancouver, British Columbia) between June 1995 and July 2009 were reviewed for cases in which weaning or transition from intravenous epoprostenol was attempted. The Cochrane Collaboration, Cochrane Register of Controlled Trials, Journals@Ovid, MEDLINE, EMBASE and Papers First were searched using predefined key words for publications describing transition of PAH patients from parenteral prostanoids to oral or subcutaneous agents.
Of the six patients who attempted, all transitioned successfully to oral or subcutaneous agents, having been on intravenous epoprostenol for a mean of 3.8 years (range 1.8 to 9.75 years). Five are living, surviving a mean of 5.5 years after transition. The literature search yielded nine studies and, of 127 patients described, 82 transitioned successfully. The length of pretransition prostanoid treatment (range 1.7 to 7.6 years) and the posttransition follow-up period (range two months to 70 months) were shorter than for patients described in the present study.
Given the rarity of PAH, the absolute numbers of patients transitioned from intravenous epoprostenol are still low. With the advent of new therapies, these numbers will hopefully increase; continued study is necessary to identify factors that are predictive of success.
Canadian respiratory journal: journal of the Canadian Thoracic Society 05/2011; 18(3):157-62. · 1.66 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. DOI:10.1164/rccm.200910-1586OC · 13.00 Impact Factor
[Show abstract][Hide abstract] 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. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To establish clinically convenient mycophenolate limited sampling strategies (LSSs) for heart and lung transplant populations, and evaluate predictive performance of published LSSs in our heart transplant population.
Methods: Twelve-hour pharmacokinetic data from 64 thoracic transplant recipients were used to develop separate LSSs in heart and lung groups (via multiple regression analysis). Only concentrations taken on or before two hours post-dose were considered as clinically convenient LSSs, and a maximum of three concentrations were used. Seventeen and sixteen patient profiles from heart and lung transplant groups, respectively, were randomly assigned as the index groups with remaining patients serving as the validation group (16 and 15 heart and lung, respectively). Concentration and area-under-the-curve (AUC) were log-transformed to normalize the data. Predictive performances of eight published LSSs for heart transplants were also evaluated in all heart transplant recipients (n=33). Acceptable bias and precision were deemed to be 15%.
Results: No LSS from the heart transplant group satisfied the pre-defined criteria for an acceptable LSS. The best LSSs for both transplant populations were developed from the lung transplant group data; equations (LogC1.5,C2) and (LogC0,C1.5) were the best candidates for the heart and lung transplant population, respectively:
LogAUC = 0.1817LogC1.5 + 0.4994LogC2 + 1.1132; r2=0.804, %bias=-3.30% and %precision=11.12%
LogAUC = 0.1677LogC0 + 0.5657LogC1.5 + 1.0830; r2=0.806, %bias=4.71% and %precision=11.79%.
The predictive performance of eight published LSS equations in our heart transplant population yielded less optimal results; %bias and %precision ranged from 6.5030.62%, and 20.4468.00%, respectively.
Conclusions: Minimally biased, highly precise and convenient LSSs for predicting MPA exposure were developed in lung transplant recipients; these LSSs also performed well when applied to the heart transplant population, whereas other published LSSs developed in heart transplant recipients yielded less optimal results when applied to our population. LSSs appear to be center-specific and should be re-validated before use.
2009 American College of Clinical Pharmacy Annual Meeting; 10/2009