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ABSTRACT: Reactive airway disease predisposes patients to episodes of acute smooth muscle mediated bronchoconstriction. We have for the first time recently demonstrated the expression and function of endogenous ionotropic GABA(A) channels on airway smooth muscle cells. We questioned whether endogenous GABA(A) channels on airway smooth muscle could augment beta-agonist-mediated relaxation. Guinea pig tracheal rings or human bronchial airway smooth muscles were equilibrated in organ baths with continuous digital tension recordings. After pretreatment with or without the selective GABA(A) antagonist gabazine (100 muM), airway muscle was contracted with acetylcholine or beta-ala neurokinin A, followed by relaxation induced by cumulatively increasing concentrations of isoproterenol (1 nM to 1 muM) in the absence or presence of the selective GABA(A) agonist muscimol (10-100 muM). In separate experiments, guinea pig tracheal rings were pretreated with the large conductance K(Ca) channel blocker iberiotoxin (100 nM) after an EC(50) contraction with acetylcholine but before cumulatively increasing concentrations of isoproterenol (1 nM to 1 uM) in the absence or presence of muscimol (100 uM). GABA(A) activation potentiated the relaxant effects of isoproterenol after an acetylcholine or tachykinin-induced contraction in guinea pig tracheal rings or an acetylcholine-induced contraction in human endobronchial smooth muscle. This muscimol-induced potentiation of relaxation was abolished by gabazine pretreatment but persisted after blockade of the maxi K(Ca) channel. Selective activation of endogenous GABA(A) receptors significantly augments beta-agonist-mediated relaxation of guinea pig and human airway smooth muscle, which may have important therapeutic implications for patients in severe bronchospasm.
AJP Lung Cellular and Molecular Physiology 10/2008; 295(6):L1040-7. · 3.66 Impact Factor
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ABSTRACT: There continues to be debate concerning which thymectomy technique is the procedure of choice in the treatment of nonthymomatous myasthenia gravis (MG). The debate persists primarily because of the lack of controlled prospective studies but also because of the varying presentations and clinical courses of MG patients. Analysis has been complicated by the absence, until very recently, of accepted objective definitions of severity of the illness and response to therapy as well as variable patient selection, timing of surgery, type of surgery, and methods of analysis of results. Without resolution of these issues by properly designed prospective studies, there can be no unequivocally valid comparison of the various thymectomy techniques. In this review, attempts have been made to clarify some of the controversial issues concerning the selection of a thymectomy technique in the treatment of nonthymomatous MG and to make limited recommendations based on the best available evidence.
Annals of the New York Academy of Sciences 07/2008; 1132:315-28. · 3.15 Impact Factor
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ABSTRACT: Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABA(A)) channels and metabotropic (GABA(B)) receptors. GABA(A) channels are ubiquitously expressed in neuronal tissues, and in mature neurons modulate an inward chloride current resulting in neuronal inhibition due to membrane hyperpolarization. In airway smooth muscle (ASM) cells, membrane hyperpolarization favors smooth muscle relaxation. Although GABA(A) channels and GABA(B) receptors have been functionally identified on peripheral nerves in the lung, GABA(A) channels have never been identified on ASM itself. We detected the mRNA encoding of the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, delta-, gamma(1-3)-, pi-, and theta-subunits in total RNA isolated from native human and guinea pig ASM and from cultured human ASM cells. Selected immunoblots identified the GABA(A) alpha(4)-, alpha(5)-, beta(3)-, and gamma(2)-subunit proteins in native human and guinea pig ASM and cultured human ASM cells. The GABA(A) beta(3)-subunit protein was immunohistochemically localized to ASM in guinea pig tracheal rings. While muscimol, a specific GABA(A) channel agonist, did not affect the magnitude or the time to peak contractile effect of substance P, it directly concentration dependently relaxed a tachykinin-induced contraction in guinea pig tracheal rings, which was inhibited by the GABA(A)-selective antagonist gabazine. Muscimol also relaxed a contraction induced by an alternative contractile agonist histamine. These results demonstrate that functional GABA(A) channels are expressed on ASM and suggest a novel therapeutic target for the relaxation of ASM in diseases such as asthma and chronic obstructive lung disease.
AJP Lung Cellular and Molecular Physiology 07/2008; 294(6):L1206-16. · 3.66 Impact Factor
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Nadine Al-Naamani,
Omar H Maarouf,
Vivek N Ahya,
David J Lederer,
James D Mendez,
Jessie S Wilt,
Alden M Doyle,
Debbie Rybak,
Frank D'Ovidio, Joshua R Sonett,
Selim M Arcasoy,
Thomas L Nickolas,
Steven M Kawut
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ABSTRACT: Glomerular filtration rate (GFR) is the best measure of kidney function; however, 24-hour creatinine clearance (CrCl) is the initial screening test used for lung transplant candidates at most centers. Although creatinine-based formulas that estimate GFR have been derived, none have been validated in patients with severe lung disease.
We performed a retrospective cohort study of patients evaluated for lung transplantation at Columbia Presbyterian Medical Center and compared the GFR estimated from the Modification of Diet in Renal Disease (MDRD) and other formulas to the CrCl. We then validated these results in a cohort of patients evaluated at the Hospital of the University of Pennsylvania.
There were strong and statistically significant direct correlations between estimated GFR and CrCl. An estimated GFR of <95 ml/min by the MDRD was very sensitive at detecting kidney dysfunction by CrCl in the derivation cohort. In the validation cohort, the negative predictive value of this cut-off was 97%.
Established formulas for estimating GFR are highly discriminating for kidney dysfunction in patients being evaluated for lung transplantation and may actually have greater validity than CrCl in some instances.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 06/2008; 27(6):635-41. · 3.54 Impact Factor
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David I Sternberg,
Daichi Shimbo,
Steven M Kawut,
Joydeep Sarkar,
Georg Hurlitz,
Frank D'Ovidio,
David J Lederer,
Jessie S Wilt,
Selim M Arcasoy,
David J Pinsky,
Jeanine M D'Armiento, Joshua R Sonett
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ABSTRACT: During lung transplantation, cells in the pulmonary parenchyma are subjected to ischemia, hypothermic storage, and reperfusion injury. Platelets, whose granular contents include adhesion receptors, chemokines, and coactivating substances that activate inflammatory and coagulant cascades, likely play a critical role in the lung allograft response to ischemia and reperfusion. The platelet response to the pulmonary allograft, however, has never been studied. Here we report significant platelet activation immediately after lung transplantation.
We performed a prospective cohort study comparing markers of platelet activation in patients undergoing lung transplantation and patients undergoing nontransplant thoracotomy. Plasma levels of soluble P-selectin, soluble CD40 ligand, and platelet-leukocyte conjugates were measured before surgery, after skin closure, and at 6 postoperative hours.
Both soluble P-selectin and soluble CD40 ligand levels increased significantly after lung transplantation but not after thoracotomy. Additionally, platelet-monocyte conjugate fluorescence was significantly higher after lung transplantation than after thoracotomy alone.
These findings suggest that platelet activation is significantly increased after lung transplantation beyond that expected from the postoperative state. The increase in circulating platelet-monocyte conjugates suggests an important interaction between platelets and inflammatory cells. Further research should examine whether platelet activation affects early graft function after lung transplantation.
The Journal of thoracic and cardiovascular surgery 04/2008; 135(3):679-84. · 3.41 Impact Factor
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ABSTRACT: Blacks with chronic illness have poorer outcomes than whites in the United States. The health outcomes of minorities with chronic obstructive pulmonary disease (COPD) on the lung transplant waiting list have not been studied.
To compare outcomes of black and white patients with COPD after listing for lung transplantation in the United States.
Retrospective cohort study of all 280 non-Hispanic black and 5,272 non-Hispanic white adults 40 years and older with COPD listed for lung transplantation in the United States between 1995 and 2004.
Blacks with COPD were more likely to have pulmonary hypertension, obesity, and diabetes; to lack private health insurance; and to live in poorer neighborhoods than whites. Blacks were less likely to undergo transplantation after listing compared with whites, despite adjustment for age, lung function, pulmonary hypertension, cardiovascular risk factors, insurance coverage, and poverty level (adjusted hazard ratio, 0.83; 95% confidence interval, 0.70-0.98; P = 0.03). This was accompanied by a greater risk of dying or being removed from the list among blacks (unadjusted hazard ratio, 1.31; 95% confidence interval, 1.05-1.63; P = 0.02).
After listing for lung transplantation, black patients with COPD were less likely to undergo transplantation and more likely to die or be removed from the list compared with white patients. Unequal access to care may have contributed to these differences.
American Journal of Respiratory and Critical Care Medicine 03/2008; 177(4):450-4. · 11.08 Impact Factor
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ABSTRACT: Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown.
To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and to determine the predictors of the risk of death after lung retransplantation.
We performed a retrospective cohort study of patients who underwent lung retransplantation between January 2001 and May 2006 in the United States (modern retransplant cohort). The characteristics and survival of this cohort were compared with those of patients who underwent first lung retransplantation between January 1990 and December 2000 (historical retransplant cohort) and patients who underwent initial lung transplantation between January 2001 and May 2006 (modern initial transplant cohort).
Modern retransplant recipients (n = 205) had a lower risk of death compared with that of the historical retransplant cohort (n = 184) (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = 0.006). However, modern retransplant recipients had a higher risk of death than that of patients who underwent initial lung transplantation (n = 5,657) (hazard ratio, 1.3; 95% confidence interval, 1.2-1.5; P = 0.001), which appeared to be explained by a higher prevalence of certain comorbidities. Retransplantation at less than 30 days after the initial transplant procedure was associated with worse survival.
Outcomes after lung retransplantation have improved; however, retransplantation continues to pose an increased risk of death compared with the initial transplant procedure. Retransplantation early after the initial transplant poses a particularly high mortality risk.
American Journal of Respiratory and Critical Care Medicine 02/2008; 177(1):114-20. · 11.08 Impact Factor
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Mark J Russo,
David I Sternberg,
Kimberly N Hong,
Robert A Sorabella,
Alan J Moskowitz,
Annetine C Gelijns,
Jessie R Wilt,
Frank D'Ovidio,
Steve M Kawut,
Selim M Arcasoy, Joshua R Sonett
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ABSTRACT: The purpose of this study was to assess (1) the relationship between donor-recipient cytomegalovirus (CMV) serologic status and posttransplant survival in the current era and (2) temporal changes in posttransplant survival by CMV matching status.
De-identified data were obtained from the United Network for Organ Sharing. Based on pretransplant CMV serologic status (+ or -) of recipients (R) and donors (D), posttransplant survival was compared among three groups: D+ /R-, D+/- /R+, and D- /R-. Primary analysis focused on transplants performed January 1, 2000 to December 31, 2004, in recipients 18 years of age or older. To assess temporal trends in survival among groups, all lung transplants occurring between January 1, 1990, and December 31, 2004, were considered and divided into three periods based on transplant year: 1990 through 1994, 1995 through 1999, and 2000 through 2004. The primary outcome measure was survival, reported as rate of death per 100 patient-years. Kaplan-Meier analysis with log-rank test was used for time-to-event analysis.
During the current era (2000 through 2004), D+ /R- (n = 951), D+/- /R+ (n = 2,676), and D- /R- (n = 772) exhibited no differences in survival (p = 0.561), with rates of death per 100 patient-years of 16.6 (95% confidence interval, 14.9 to 18.5), 15.0 (95% confidence interval, 14.0 to 16.0), and 14.7 (95% confidence interval, 13.0 to 16.6), respectively. However, survival was significantly different for groups in the earlier eras of 1990 through 1994 (p < 0.001) and 1995 through 1999 (p < 0.001). During the three periods, survival improved significantly in D+ /R- (p < 0.001) and D+/- /R+ (p < 0.001), but survival in D- /R- (p = 0.351) did not change significantly with time.
In the current era, survival after lung transplantation is statistically equivalent regardless of CMV match status. Although in previous eras survival was worse among the D+/- /R+ and D+ /R- groups, in this era of aggressive CMV prophylaxis, CMV mismatch should not be sufficient grounds to decline a lung allograft offer.
The Annals of thoracic surgery 10/2007; 84(4):1129-34; discussion 1134-5. · 3.74 Impact Factor
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Hilary A Yegen,
David J Lederer,
R Graham Barr,
Jessie S Wilt,
Yixin Fang,
Emilia Bagiella,
Frank D'Ovidio,
Jeffrey M Okun, Joshua R Sonett,
Selim M Arcasoy,
Steven M Kawut
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ABSTRACT: The risk factors for venous thromboembolism (VTE) following lung transplantation are not well established. We aimed to estimate the incidence of VTE and to identify the risk factors for VTE after lung transplantation.
We performed a nested case-control study within the cohort of 121 patients who underwent lung transplantation at our center between August 2001 and July 2005. Control subjects were matched to case patients on the number of days from the time of transplant. Cox proportional hazards models were used to identify risk factors for VTE.
Twenty-four patients had deep vein thromboses, and 6 patients had pulmonary emboli (3 patients had both) [22% of the cohort]. In multivariate models, older age (p < 0.05), diabetes mellitus (p = 0.03), and pneumonia (p = 0.02) were associated with a higher rate of VTE.
VTE is a frequent complication of lung transplantation. Older age, diabetes, and pneumonia increase the rate of VTE. Future studies of intensive VTE prophylaxis may be warranted.
Chest 09/2007; 132(2):547-53. · 5.25 Impact Factor
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The Annals of thoracic surgery 08/2007; 84(1):360-1; author reply 361. · 3.74 Impact Factor
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ABSTRACT: Almost 125 years after the first documented case, pulmonary metastasectomy is still poorly understood. No other organ is subject to the wide histologic variety of metastatic insults, and this fact has complicated a complete exposition of when pulmonary metastasectomy may be beneficial. Many physicians still consider pulmonary metastatic disease to be always incurable, and they may underestimate existing surgical options including the benefits of pulmonary metastasectomy. In addition, technological improvements in radiological screening of pulmonary metastases and thoracoscopic resection are fundamentally altering the management of these patients and their surgery. This article reviews the history, form, and future of pulmonary metastasectomy, the literature that supports or refutes its application in various tumor types, and the screening and surgical evaluation that is needed prior to its performance.
Seminars in Oncology 07/2007; 34(3):186-96. · 3.50 Impact Factor
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David J Lederer,
Byron M Thomashow,
Mark E Ginsburg,
John H M Austin,
Matthew N Bartels,
Chun K Yip,
Patricia A Jellen,
Frances L Brogan,
Steven M Kawut,
Roger A Maxfield,
Angela M DiMango,
Paul F Simonelli,
Lyall A Gorenstein,
Gregory D N Pearson, Joshua R Sonett
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ABSTRACT: We hypothesized that lung-volume reduction surgery for pulmonary emphysema would improve body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index, a multidimensional predictor of survival in chronic obstructive pulmonary disease. We also aimed to identify preoperative predictors of improvement in the BODE index.
In a prospective cohort study of patients undergoing lung-volume reduction surgery at our center, with the methodology of the National Emphysema Treatment Trial, we compared clinical characteristics before and 1 year after surgery with the Wilcoxon signed rank test. Changes in the BODE index were correlated with preoperative variables with the Spearman correlation coefficient.
Twenty-three patients with predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy). There were no postoperative or follow-up deaths. The BODE index improved from a median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2-4) 1 year after surgery (P < .0001). Improvements were seen in the lung function and dyspnea components of the BODE index. Lower preoperative 6-minute walk distance and lower postwalk Borg fatigue scores were each associated with greater improvement in the BODE index after 1 year.
Lung-volume reduction surgery for pulmonary emphysema improved the BODE index in patients with predominantly upper-lobe disease. Lower preoperative 6-minute walk distance correlated with greater improvement in the BODE index.
The Journal of thoracic and cardiovascular surgery 06/2007; 133(6):1434-8. · 3.41 Impact Factor
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ABSTRACT: Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary arterial hypertension with no effective medical therapy and a high risk of mortality. The pathogenesis of PCH is unknown.
We used gene expression analysis to compare lung tissue samples from two patients with PCH to those from seven control subjects. The nodules of proliferating capillaries in PCH patients were needle microdissected from cryostat sections. RNA extraction and labeling were followed by hybridization to U95Av2 oligonucleotide arrays (Affymetrix; Santa Clara, CA). In situ hybridization and immunohistochemistry were also performed.
The gene expression profile of PCH allowed for unsupervised clustering from the profile of the lung tissue samples of control subjects. Platelet-derived growth factor (PDGF)-B gene (PDGFB), PDGF receptor (PDGFR)-beta gene (PDGFR-beta), mast cell-related genes, and type 2 pneumocyte-related genes were found to be overexpressed in PCH lesions. In situ hybridization as well as immunohistochemistry for PDGFB showed expression by type 2 pneumocytes and endothelial cells. Immunohistochemical staining for PDGFR-beta localized to pericytic/vascular smooth muscle cells surrounding the proliferating capillaries. CD117 staining confirmed an abundance of mast cells in the lesions, which also stained heavily for PDGFR-beta.
The expression of the PDGFB and PDGFR-beta genes characterizes the nodular proliferations of PCH. Increased numbers of mast cells, pericytes, and type II pneumocytes accompany the endothelial proliferation. The up-regulation of these important angiogenic and antiapoptotic genes suggests a mechanism and potential therapeutic approaches for PCH.
Chest 04/2007; 131(3):850-5. · 5.25 Impact Factor
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ABSTRACT: We report the case of a 15-year-old girl with cystic fibrosis and rapidly declining pulmonary function tests who was found to have collapse of the left main bronchus from bronchomalacia. She underwent successful deployment of an expandable silicone stent in the collapsed bronchus, after which her pulmonary function test results and her clinical picture markedly improved, obviating the need for immediate transplantation. A literature review yielded no prior reports of bronchomalacia in a cystic fibrosis patient being treated with a silicone stent. This case shows that a simple, effective treatment is possible for one cause of obstructive pulmonary function in cystic fibrosis.
The Annals of thoracic surgery 01/2007; 82(6):2268-70. · 3.74 Impact Factor
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ABSTRACT: gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABA(A)/GABA(C)) and metabotropic (GABA(B)) receptors (R). In addition to their location on neurons, GABA and functional GABA(B) receptors have been detected in nonneuronal cells in peripheral tissue. Although the GABA(B)R has been shown to function as a prejunctional inhibitory receptor on parasympathetic nerves in the lung, the expression and functional coupling of GABA(B) receptors to G(i) in airway smooth muscle itself have never been described. We detected the mRNA encoding multiple-splice variants of the GABA(B)R1 and GABA(B)R2 in total RNA isolated from native human and guinea pig airway smooth muscle and from RNA isolated from cultured human airway smooth muscle (HASM) cells. Immunoblots identified the GABA(B)R1 and GABA(B)R2 proteins in human native and cultured airway smooth muscle. The GABA(B)R1 protein was immunohistochemically localized to airway smooth muscle in guinea pig tracheal rings. Baclofen, a GABA(B)R agonist, elicited a concentration-dependent stimulation of [(35)S]GTPgammaS binding in HASM homogenates that was abrogated by the GABA(B)R antagonist CGP-35348. Baclofen also inhibited adenylyl cyclase activity and induced ERK phosphorylation in HASM. Another GABA(B)R agonist, SKF-97541, mimicked while pertussis toxin blocked baclofen's effect on ERK phosphorylation, implicating G(i) protein coupling. Functional GABA(B) receptors are expressed in HASM. GABA may modulate an uncharacterized signaling cascade via GABA(B) receptors coupled to the G(i) protein in airway smooth muscle.
AJP Lung Cellular and Molecular Physiology 12/2006; 291(5):L923-31. · 3.66 Impact Factor
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ABSTRACT: Functional studies may be useful to predict survival in idiopathic pulmonary fibrosis (IPF). Various cutoffs of 6-min-walk distance (6MWD) have been suggested to identify patients at a high risk of death.
To examine the association between 6MWD and survival in patients with IPF listed for lung transplantation, and to identify sensitive and specific cutoffs for predicting death at 6 mo.
We performed a retrospective cohort study of 454 patients classified as having IPF listed for lung transplantation with the United Network for Organ Sharing between June 30, 2004 and July 22, 2005.
Lower 6MWD was associated with an increased mortality rate (p value for linear trend < 0.0001). Patients with a walk distance less than 207 m had a more than fourfold greater mortality rate than those with a walk distance of 207 m or more, despite adjustment for demographics, anthropomorphics, FVC % predicted, pulmonary hypertension, and medical comorbidities (adjusted rate ratio, 4.7; 95% confidence interval, 2.5-8.9; p < 0.0001). 6MWD was a significantly better predictor of 6-mo mortality than was FVC % predicted (c-statistic = 0.73 vs. 0.59, respectively; p = 0.02).
Lower 6MWD was strongly and independently associated with an increased mortality rate for wait-listed patients classified as having IPF. 6MWD was a better predictor of death at 6 mo than was FVC % predicted.
American Journal of Respiratory and Critical Care Medicine 09/2006; 174(6):659-64. · 11.08 Impact Factor
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ABSTRACT: The determinants of immunoglobulin G (IgG) level and the risk of hypogammaglobulinemia (HGG) in patients with severe lung disease before and after lung transplantation are unknown.
We aimed to identify predictors of low IgG levels before and after lung transplantation.
We performed a retrospective cohort study of 40 consecutive lung transplant recipients at our center. Total IgG levels were measured before and serially after transplantation. Mild HGG was defined as IgG levels from 400-699 mg/dl; severe HGG was defined as IgG levels<400 mg/dl.
Before transplantation, six (15%) patients had mild HGG, and none had severe HGG. Patients with chronic obstructive pulmonary disease had lower IgG levels compared with patients with other diseases (independent of corticosteroid use and age; p=0.001) and an increased risk of mild HGG (p=0.005). The cumulative incidences of mild and severe HGG significantly increased after transplantation (58 and 15%, respectively, both p<0.04 compared with pretransplant prevalences). Lower pretransplant IgG level and treatment with mycophenolate mofetil were associated with lower IgG levels after transplantation (both p<0.05). Only lower pretransplant IgG levels were significantly associated with an increased risk of severe HGG after transplantation (p=0.02).
Mild HGG is common in patients with severe chronic obstructive pulmonary disease, and the incidences of mild and severe HGG increase significantly early after lung transplantation. Baseline IgG levels and treatment with mycophenolate mofetil affect post-transplant IgG levels.
American Journal of Respiratory and Critical Care Medicine 04/2006; 173(8):917-21. · 11.08 Impact Factor
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ABSTRACT: There are no studies focused on skeletal status in patients with diffuse parenchymal lung disease (DPLD). We hypothesized that patients with DPLD referred for lung transplantation would have a high prevalence of osteoporosis related to corticosteroid use or reduced pulmonary function and exercise capacity.
Retrospective cohort study.
Tertiary care center.
Eighty-six patients with DPLD referred to our center for lung transplantation evaluation between March 1999 and April 2004.
Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and radius at the time of referral. Criteria developed by the World Health Organization were used to define osteopenia and osteoporosis. Fifty-five patients (64%) had usual interstitial pneumonia-pattern lung disease, 14 patients (16%) had nonspecific interstitial pneumonia-pattern lung disease, and 17 patients (20%) had other forms of DPLD. Sixty-four patients (74%) were receiving corticosteroids, and 43 patients (50%) were receiving preventive therapy for osteoporosis. Eleven patients (13%; 95% confidence interval [CI], 7 to 22%) met criteria for osteoporosis at any site, and 49 patients (57%; 95% CI, 46 to 68%) had osteopenia. Lower body mass index (BMI) [adjusted odds ratio (OR), 1.3; 95% CI, 1.1 to 1.6; p = 0.007] and Hispanic ethnicity (adjusted OR, 9.7; 95% CI, 1.8 to 52; p = 0.008) were independently associated with an increased risk of osteoporosis. Linear regression analysis confirmed that BMD at the femoral neck and hip was directly associated with BMI (p < 0.002). These findings were not affected by adjustment for the use of corticosteroids or osteoporosis prophylaxis, pulmonary function, or exercise performance.
Reduced BMD was common in patients with DPLD who were referred for lung transplantation. Lower BMD was associated with lower BMI, whereas there was no association with other clinical factors in our cohort. Hispanic patients with DPLD had a higher risk of osteoporosis than non-Hispanic patients, independent of other variables. Given their increased risk of bone loss, patients with DPLD should undergo screening for osteoporosis and receive prophylaxis and treatment according to published guidelines.
Chest 02/2006; 129(1):140-6. · 5.25 Impact Factor
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Chest 01/2006; 128(6 Suppl):575S-5766S. · 5.25 Impact Factor
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ABSTRACT: Diffuse parenchymal lung disease is associated with a high risk of mortality despite early referral and listing for lung transplantation. We hypothesized that cardiopulmonary exercise test results and the distance walked in 6min (6MWTD) would be associated with survival in patients with diffuse parenchymal lung disease referred for lung transplantation.
Retrospective cohort study.
Tertiary care center.
We included 51 consecutive patients with diffuse parenchymal lung disease who underwent exercise testing after referral to the Lung Transplant Program at the New York Presbyterian Hospital between January 2000 and December 2002. Thirty-three patients were listed, and 7 underwent transplantation during the study period. There were 17 deaths with 1 death post-transplantation.
A 6MWTD < 350 m was associated with an increased risk of death (HR = 4.6, 95% CI 1.5-14.2, P = 0.009). Oxygen saturation with unloaded exercise (HR = 0.91, 95% CI 0.84-0.98, P = 0.015) and oxygen consumption at peak exercise adjusted for weight (HR = 0.88, 95% CI 0.79-0.99, P = 0.039) were also associated with the risk of death. A patient with oxygen saturation <95% during unloaded exercise had a 75% chance of dying on the list for transplantation. A patient with 6MWTD < 350 m had a 67% chance of dying on the list.
Cardiopulmonary exercise test parameters and the 6MWTD were associated with the risk of death. Measures during exercise may be useful for determination of prognosis and for prioritizing patients with diffuse parenchymal lung disease for lung transplantation.
Respiratory Medicine 12/2005; 99(11):1431-9. · 2.47 Impact Factor
