Decrease In DLCO Research Articles

Potential Airway Obstruction 7 years Following Exposure to Chlorine

Background: On January 6, 2005 there was a train derailment which released~54,430 kg of chlorine into the town of Graniteville, SC, USA, population~7,000. Aim: To assess long-term pulmonary health effects of a single high-concentration exposure to chlorine gas. Methods: Since summer 2012 diagnostic pulmonary function tests with single breath carbon monoxide diffusing capacity(DLCO) are being provided to 600 former Graniteville cotton mill workers to assess long-term health consequences of chlorine exposure(N to-date= 83). Demographic information, respiratory symptoms, exposure and smoking history abstracted from occupational records before the chlorine release are being linked to prospective health assessments. Preliminary data for participants whose lung volumes and DLCOs met ATS criteria were included (lung volumes: n=65, 19/46 exposed/unexposed, DLCO: n=72, 20/52 exposed/ unexposed). Mean percent predicted measures for pulmonary function parameters and DLCO adjusted for hemoglobin were compared between exposed and unexposed millworkers using Fisher exact and T-test. Results: We found a significant increase in percent predicted residual volume (RV) and total lung capacity (TLC) in exposed millworkers (p=0.02). The proportion of millworkers with lower predicted FEV1/FVC ratio was significantly higher in exposed than in unexposed (p<.0001). There were 7/19(37%) exposed who have FEV1/FVC ratio less than 70% of predicted as compared to 3/46(6.5%) unexposed and 10/19(53%) exposed who had FEV1/FVC ratio less than 75% of predicted as compared to 9/46(20%) unexposed. Four of 20 exposed (20%) showed a moderate decrease in DLCO as compared to 6 of 52 unexposed (11%). Conclusion: Our preliminary findings suggested that inhalation of high concentration chlorine increased RV and TLC and decreased FEV1/FVC ratio 7 years after exposure, indicators of airway obstruction or destroyed alveolar septa leading to emphysema like changes. Further research is needed to discern the mechanism behind these changes.

Annual changes in pulmonary function in combined pulmonary fibrosis and emphysema: Over a 5-year follow-up

Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder that has been previously described, and the distinct features of CPFE in comparison with chronic obstructive pulmonary disease (COPD) have been reported. However, the yearly dynamics of pulmonary function parameters in CPFE patients compared with those in COPD patients have not yet been reported. We retrospectively enrolled patients with CPFE and COPD who had undergone pulmonary function tests more than five times during a follow-up period of more than five years. The baseline clinical characteristics and the annual changes in pulmonary function during the follow-up period in 16 stable CPFE patients were compared with those in 19 stable COPD patients. Annual changes in pulmonary function were estimated from linear regressions, with assumptions for time-dependency and linearity. We analyzed the time-dependent fluctuations in pulmonary function for the two disorders. Annual decreases in VC and FVC in the CPFE group were significantly higher than those in the COPD group. Annual decrease in FEV1/FVC in the COPD group was significantly higher than in the CPFE group. During the follow-up period, FEV1/FVC in the CPFE group appeared to improve because of annual decrease in FVC. Annual decreases in DLco and DLco/VA in the CPFE group were significantly higher than those in the COPD group. This is the first report showing the yearly dynamics of pulmonary function parameters in CPFE patients compared with those in COPD patients during a follow-up period of more than five years. This study revealed that the physiologic consequences of CPFE including the rate of progression of pulmonary function impairment were different from those of COPD.

Phase II multicenter clinical trial of isolated lung perfusion (ILuP) with melphalan (MN) in patients (pts) with resectable lung metastases (LM).

7534 Background: Five-year overall survival (OS) of pts undergoing surgical resection of LM from colorectal cancer (CRC) and sarcoma remains low [20-50%]. Local recurrence rate is high, even after complete surgical resection [48-66%] (Pastorino et al, 1997). Combined modality therapy is currently evaluated. ILuP allows the delivery of high-dose locoregional chemotherapy without systemic exposure. In a previous phase I study maximum tolerated dose of MN was found to be 45mg at a perfusion temperature of 37°C (Grootenboers et al, 2007). Methods: From 2006 to 2011 50 pts, 28 male, median age 57 years [15-76], with LM from CRC [n=30] or sarcoma [n=20] were included in a phase II clinical trial conducted in 4 cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, followed by resection of all palpable LM. Survival was calculated according to the Kaplan-Meier method. Results: Operative mortality was 0%, 90-day morbidity was mainly cardiac [grade 3: 2%] and respiratory [grade 3: 29%, grade 4: 2%]. After a median follow-up of 24 months [3-63 mos] 18 pts died, 2 without recurrence. Seven pts [14%] had their initial recurrence in the perfused lung. Initial progressive disease outside the perfused lung occurred in 23 pts [46%]; contralateral, non-perfused lung 10, liver 3, brain 2, primary site 1 and other location 7. OS and disease-free survival (DFS) are shown in table 1. Lung function data showed a decrease in FEV1 and DLCO of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 mos, respectively, compared to preoperative values. Long-term quality of life evolution after ILuP and lung metastasectomy was comparable with a standard lung metastasectomy by thoracotomy in one participating center (Balduyck et al, 2012). Conclusions: Compared to historical series of LM resection without ILuP favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in pts with resectable LM from CRC or sarcoma. Clinical trial information: 2006-002808-34. [Table: see text]

Tomographic and functional findings in severe COPD: comparison between the wood smoke-related and smoking-related disease

OBJECTIVE: Wood smoke exposure is a risk factor for COPD. For a given degree of airway obstruction, the reduction in DLCO is smaller in individuals with wood smoke-related COPD than in those with smoking-related COPD, suggesting that there is less emphysema in the former. The objective of this study was to compare HRCT findings between women with wood smoke-related COPD and women with smoking-related COPD. METHODS: Twenty-two women with severe COPD (FEV1/FVC ratio < 70% and FEV1 < 50%) were divided into two groups: those with wood smoke-related COPD (n = 12) and those with smoking-related COPD (n = 10). The two groups were compared regarding emphysema scores and airway involvement (as determined by HRCT); and functional abnormalities-spirometry results, DLCO, alveolar volume (VA), the DLCO/VA ratio, lung volumes, and specific airway resistance (sRaw). RESULTS: There were no significant differences between the two groups in terms of FEV1, sRaw, or lung hyperinflation. Decreases in DLCO and in the DLCO/VA ratio were greater in the smoking-related COPD group subjects, who also had higher emphysema scores, in comparison with the wood smoke-related COPD group subjects. In the wood smoke-related COPD group, HRCT scans showed no significant emphysema, the main findings being peribronchial thickening, bronchial dilation, and subsegmental atelectasis. CONCLUSIONS: Female patients with severe wood smoke-related COPD do not appear to develop emphysema, although they do show severe airway involvement. The reduction in DLCO and VA, with a normal DLCO/VA ratio, is probably due to severe bronchial obstruction and incomplete mixing of inspired gas during the determination of single-breath DLCO.

Decline in pulmonary function during chronic hepatitis C virus therapy with modified interferon alfa and ribavirin

Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg-IFNα-2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research.

The rise in carboxyhemoglobin from repeated pulmonary diffusing capacity tests

The purpose of this study determined the rise in carboxyhemoglobin percentage (COHb) from repeated pulmonary diffusing capacity tests using 5 or 10s single breath-hold maneuvers. Five male and four female non-smokers [baseline COHb=1.2 (SD 0.5%)] performed repeated pulmonary diffusing capacity testing on two separate days. The days were randomized to either repeated 10s (0.28% CO), or 5s (0.28% CO, 55ppm NO) breath-hold maneuvers. Twenty-two 5s breath-hold maneuvers, each separated by 4min rest, raised COHb to 11.1 (1.4)% and minimally raised the methemoglobin percentage (METHb) by 0.3 (0.2)% to a value of 0.8 (0.2)%. After the 22nd test, pulmonary diffusing capacity for carbon monoxide (DLCO) was reduced by about 4mL/min/mmHg, equating to a 0.44% increase in COHb per 5s breath-hold maneuver and a concomitant 0.35mL/min/mmHg decrease in DLCO. Pulmonary diffusing capacity for nitric oxide (DLNO) was not altered after 22 tests. On another day, the 10s single breath-hold maneuver increased COHb by 0.64% per test, and reduced DLCO by 0.44mL/min/mmHg per test. In conclusion, 5s breath-hold maneuvers do not appreciably raise METHb or DLNO, and DLCO is only significantly reduced when COHb is at least 6%.

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles

BackgroundIncreased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease.ObjectivesTo characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure to concentrated ambient fine particles (CAFP) with MMAD ≤ 2.5 microns in ex-smokers and lifetime smokers.MethodsEleven subjects, aged 35–74 years, came to the laboratory 5 times; a training day and two exposure days separated by at least 3 weeks, each with a post-exposure visit 22 h later. Double-blind and counterbalanced exposures to “clean air” (mean 1.5 ± 0.6 μg/m3) or CAFP (mean 108.7 ± 24.8 μg/m3 ) lasted 2 h with subjects at rest.ResultsAt 3 h post-exposure subjects’ DTPA clearance half-time significantly increased by 6.3 min per 100 μg/m3 of CAFP relative to “clean air”. At 22 h post-exposure they showed significant reduction of 4.3% per 100 μg/m3 in FEV1 and a significant DLCO decrease by 11.1% per 100 μg/m3 of CAFP relative to “clean air”. At both 3 h and 22 h the HDL cholesterol level significantly decreased by 4.5% and 4.1%, respectively. Other blood chemistries and markers of lung injury, inflammation and procoagulant activity were within the normal range of values at any condition.ConclusionsThe results suggest that an acute 2 h resting exposure of smokers and ex-smokers to fine ambient particulate matter may transiently affect pulmonary function (spirometry and DLCO) and increase DTPA clearance half-time. Except for a post exposure decrease in HDL no other markers of pulmonary inflammation, prothrombotic activity and lung injury were significantly affected under the conditions of exposure.

Can We Predict the Severity of Pulmonary Hypertension in Patients With Scleroderma?

ObjectivesTo describe the clinical–biological characteristics of patients with scleroderma (SS) and pulmonary artery hypertension (PAH).To establish the relationship between pulmonary functional tests (PFT), Doppler echocardiography (ECHO) and the severity of the PAH. Material and methodsRetrospective study of patients with SS treated at a tertiary center. All participants received a protocol study, which included a complete analysis and additional tests: ECHO and PFT with carbon monoxide diffusing capacity (DLCO). ResultsOverall, 331 patients were treated, including 68 (20.5%) with PAH. The limited subtype of SS was the most prevalent. The Pearson's correlation coefficient was used for the following variables: FVC-sPAP, FVC/DLCO-sPAP, DLCO-sPAP and TRV-sPAP, showed a significant moderate linear association in the relationship DLCO-sPAP and TRV-sPAP.29 deaths occurred, with 12 of them related to PAH. The median time between the PAH diagnosis and death was 1.8 years. ConclusionsThe decrease in DLCO and the increase in TRV are negative predictor factor of PAH which, at the same time, means a worsening prognosis for patients with SS.

Changes in Lung Function Parameters After Wedge Resections: A Prospective Evaluation of Patients Undergoing Metastasectomy

Pulmonary metastasectomy with lung-sparing local excisions is a widely accepted method of treating stage IV malignancies in selected cases. The ability to predict postoperative lung function is an unresolved issue, especially when multiple wedge resections are planned. To help develop a method to predict postoperative lung function after wedge resections, we present this prospective observational study. A total of 77 patients who underwent one or more wedge resections to remove lung metastases completed the study protocol. Spirometry results, diffusion capacity of lung for carbon monoxide (Dlco), and blood gases and potential confounding factors were measured prior to, immediately following, and 3 months after the procedure and were analyzed. Seventy-seven patients with a median age of 61.3 years underwent up to 22 wedge resections. The mean lung function losses were FVC (-7.5%), total lung capacity (TLC) (-7.9%), FEV(1) (-9.2%), and Dlco (-8.8%), and all were statistically significant (P < .001). The lung function losses also differed significantly between those having a single and those with more than eight wedge resections. Using regression analysis, we found that for every additional wedge resection, there was a reduction in FVC of 30 mL (0.7%), in TLC of 44 mL (0.65%), and in FEV(1) of 23 mL (0.58%). Metastasectomy by wedge resection significantly reduces lung function parameters. As a benchmark, we can predict a 0.6% decrease in spirometry values and Dlco for every additional wedge resection, and a decrease of approximately 5% that may be attributed to thoracotomy.

¿Podemos predecir la gravedad de la hipertensión arterial pulmonar en pacientes con esclerodermia?

To describe the clinical-biological characteristics of patients with scleroderma (SSc) and pulmonary artery hypertension (PAH). To establish the relationship between pulmonary functional tests (PFT), Doppler echocardiography (ECHO) and the severity of the PAH.Retrospective study of patients with scleroderma treated at a tertiary center. All participants received a protocol study, which included a complete analysis and additional tests: Doppler Echocardiography and pulmonary functional tests (PFT) with carbon monoxide diffusing capacity (DLCO).Overall, 331 patients were treated, including 68 (20.5%) with PAH. The limited subtype of Scleroderma was the most prevalent. The Person's correlation coefficient was used for the following variables: FVC-sPAP, FVC/DLCO-sPAP, DLCO-sPAP and TRV-sPAP, showed a significant moderate linear association in the relationship DLCO-sPAP and TRV-sPAP. 29 deaths occurred, with 12 of them related to PAH. The median time between the PAH diagnosis and death was 1.8 years.The decrease in DLCO and the increase in TRV are negative predictor factor of PAH which, at the same time, means a worsening prognosis for patients with Scleroderma.

The estimated pulmonary artery pressure can be elevated in Behçet’s syndrome

To determine the frequency of elevated systolic pulmonary artery pressure (sPAP) estimated by echocardiography in Behçet's syndrome (BS) patients with pulmonary artery involvement (PAI), in healthy controls and in diseased controls with systemic sclerosis (SSc), as well as in BS patients without PAI. We studied 3 groups of patients with BS (patients with PAI: n = 30, with vascular disease but without PAI: n = 26 and without vascular disease: n = 21), patients with SSc (n = 23) and healthy controls (n = 22). Systolic pulmonary artery pressure (sPAP) was estimated by echocardiography. The upper limit for a normal sPAP was arbitrarily set at 35 mmHg. We also evaluated cardiac function by echocardiography. Pulmonary function tests, a six-minute walking test (six-MWT) and several serum biomarkers were also studied. The frequency of patients with an elevated sPAP was significantly higher only among BS patients with PAI (17%) and among patients with SSc (26%). In addition, DL(CO) was decreased and pro-BNP levels were increased in BS patients with PAI, which are similar to the results in patients with SSc. Furthermore, BS patients with PAI also had mild RV diastolic dysfunction. When BS involves the pulmonary arteries, it can cause mild elevations in the estimated sPAP, decrease in DL(CO), mild cardiac dysfunction and increase in pro-BNP levels. These findings suggest that BS can also affect the small/micro vessels of the heart and the lungs in addition to the well-recognized large vessel disease.

Accelerated BEP for advanced germ cell tumors: An Australian multicenter phase I/II trial.

4561 Background: Standard chemotherapy for advanced germ cell tumors is BEP (bleomycin, etoposide, cisplatin). 5-year survival is > 90% in good-risk disease, but only ~80% in intermediate and ~ 60% in poor risk disease. Accelerated (dose-dense) versions of standard regimens have proven more effective in other malignancies. We aimed to determine feasibility, tolerability and activity of an accelerated version of BEP. Methods: Single arm, multi-center, phase I/II trial (n=45 recruited). Target population was patients with advanced germ cell tumours and radiologically measurable disease. Patients with elevated serum tumour markers as only evidence of disease were ineligible. Treatment was cisplatin 20mg/m2 and etoposide 100mg/m2 on days 1-5, and pegylated G-CSF 6mg on day 6, all repeated every 2 weeks for 4 cycles (3 cycles for good risk). Bleomycin was given at 30kIU weekly to a total 12 doses (9 doses for good risk). Primary endpoint was regimen feasibility. Results: Results are presented for the 1st 41 patients enrolled from February 2008 to July 2010. 10 had poor risk disease (1 female), 15 intermediate risk, 16 good risk disease. Median follow-up is 14 months (range 2 to 27). At least 36 (88%) were eligible to start a 4th cycle of BEP on schedule or with no more than 1 week delay. Adverse events are presented in table 1. 22 of 41 patients (9 of 25 patients with intermediate or poor risk, 13 of 16 patients with good risk) achieved a complete response to chemotherapy +/- surgery. 4 of 41 patients have relapsed including one death. 1 year progression-free survival is 80% for intermediate or poor risk disease, and 100% for good risk disease. 1 year overall survival is 93% for intermediate or poor risk disease, and 100% for good risk disease. Conclusions: Feasibility and adverse events appears comparable to standard BEP. Efficacy data appears promising. Results from this trial and a similar study in the UK (Williams, ASCO 2008) provide the rationale for an international trial comparing accelerated versus standard versions of BEP. Number of patients with adverse events by CTCAE v3 criteria. G1/2 G3/4 Febrile neutropenia - 5 Other infection 7 6 Anemia 19 1 Nephrotoxicity 2 0 Neurotoxicity 19 0 Hearing loss 5 0 Tinnitus 30 0 Decrease in DLCO 38 0

Angiogenic activity of sera from interstitial lung disease patients in relation to pulmonary function

ObjectiveChronic inflammation and fibrosis are characteristic of interstitial lung diseases (ILD) and are accompanied by neovascularisation. The aim of this study was to examine the relationship between the angiogenic activity of sera from ILD patients and pulmonary function tests.Material and methodsSerum samples were obtained from 225 ILD patients: 83 with sarcoidosis, 31 with idiopathic pulmonary fibrosis, 29 with extrinsic allergic alveolitis, 16 with collagen vascular diseases, 13 with scleroderma with pulmonary manifestations (SCL), 14 with Wegener's granulomatosis (WG), 12 with silicosis, 12 with pulmonary Langerhans cells histiocytosis, 10 with drug-induced pulmonary fibrosis, 5 with cryptogenic organizing pneumonia, and 36 healthy volunteers. An animal model of leukocyte induced angiogenesis assay was used as an angiogenic test. In all patients spirometry, whole body plethysmography, static lung compliance, and single breath diffusing capacity of the lungs for carbon monoxide (DLCO) were performed.ResultsThe angiogenic properties of sera from ILD differed, depending on the disease. In the examined ILD, the most important functional disturbances were decreases in static compliance and DLco. The correlation between DLCO and angiogenic activity of sera was observed (P < 0.05).ConclusionsThe data show that sera from ILD patients constitute a source of mediators modulating angiogenesis. Angiogenic activity of sera of ILD patients is related to DLCO.

Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time (IRT) compared to control. Regarding pulmonary function tests, children with JIA showed significant decrease in FVC, PEF, Pimax, Pemax and DLCO compared to normal controls. This decrease was not related to age, height or weight of these patients. There was significant inverse correlation between lung function parameters and the rheumatoid factor titer, erythrosedimentation rate, disease duration and the duration of methotrexate use (P < 0.01). Despite of an asymptomatic cardiopulmonary status, significant systolic and diastolic functional abnormalities exist in children with JIA. Also, both restrictive and obstructive lung impairments were found.

Angiogenic Activity of Sera from Extrinsic Allergic Alveolitis Patients in Relation to Clinical, Radiological, and Functional Pulmonary Changes

Extrinsic allergic alveolitis (EAA) caused by inhaled organic environmental allergens can progress to a fibrotic end-stage lung disease. Neovascularization plays an important role in pathogenesis of pulmonary fibrosis. The aim of this study was to assess the effect of sera from EAA patients on the angiogenic capability of normal peripheral human mononuclear cells (MNC) in relation to the clinical, radiological, and functional changes. The study population consisted of 30 EAA patients and 16 healthy volunteers. Routine pulmonary function tests were undertaken using ERS standards. As an angiogenic test, leukocyte-induced angiogenesis assay according to Sidky and Auerbach was used. Compared with sera from healthy volunteers, sera from our EAA patients significantly stimulated angiogenesis (P<0.001). However, sera from healthy donors also stimulated angiogenesis compared to PBS (P<0.001). No correlation was found between serum angiogenic activity and clinical symptoms manifested by evaluated patients. A decrease in DLco and in lung compliance in EAA patients was observed but no significant correlation between pulmonary functional tests and serum angiogenic activity measured by the number of microvessels or an angiogenesis index was found. However, the proangiogenic effect of sera from EAA patients differed depending on the stage of the disease and was stronger in patients with fibrotic changes. The present study suggests that angiogenesis plays a role in the pathogenesis of EAA. It could be possible that the increase in the angiogenic activity of sera from EAA patients depends on the phase of the disease.

Coexistent emphysema delays the decrease of vital capacity in idiopathic pulmonary fibrosis

Although previous authors have reported single data point, yearly changes in respiratory function have not been examined in combined pulmonary fibrosis and emphysema (CPFE). To quantify the annual changes in respiratory function of patients with CPFE and to examine the difference in survival between CPFE patients and patients with idiopathic pulmonary fibrosis without emphysema (IPF alone), 26 patients with CPFE and 33 IPF alone patients, whose respiratory function had been monitored for at least a year, were selected. The baseline of vital capacity percent predicted (VC% pred) in CPFE patients was greater than that in IPF-alone patients (86.6+/-24.0% vs. 72.8+/-19.4%, p=0.018). The annual decrease in VC% pred was significantly less in CPFE patients than in IPF-alone patients (-1.2+/-4.8% vs. -8.0+/-7.4%, p<0.001). Baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC%) in CPFE patients was lower than that in IPF-alone patients (76.6+/-8.5% vs. 85.2+/-6.7%, p<0.001). In the CPFE group, FEV(1)/FVC% tended to decrease with time (-0.5+/-2.2% per year), but, in contrast, it increased in IPF-alone patients (+1.1+/-3.4% per year) (p=0.036). Baseline of diffusing capacity percent predicted (DLco% pred) was significantly lower in CPFE patients than in IPF-alone patients (45.3+/-15.0% vs. 60.7+/-19.8%, p=0.003). The annual decrease in DLco% pred was lower in CPFE patients than in IPF-alone patients (-3.7+/-7.9% vs. -10.7+/-8.8%, p=0.042). There was no significant difference in the survival duration between 26 CPFE and 33 IPF-alone patients according to Kaplan-Meier analysis. Ventilatory and gas-exchange deterioration during the course of IPF became mild when emphysema was coexistent.

Alveolar Membrane Conductance Decreases as BNP Increases During Exercise in Heart Failure. Rationale for BNP in the Evaluation of Dyspnea

Background In left ventricular failure (LVF) patients, brain natriuretic peptide (BNP), lung diffusion for carbon monoxide (DLCO), and alveolar-membrane conductance (DM) correlate with LVF severity and prognosis. The reduction of DLCO and DM during exercise reflects pulmonary edema formation. Methods and Results To evaluate, in LVF patients, the correlation between BNP and lung diffusion parameters at rest and during exercise, we studied 17 severe LVF patients, 13 moderate, and 10 normals measuring BNP and lung diffusion parameters before, at the end, and 1 hour after a 10-minute high-intensity constant-workload exercise. At rest, a significant correlation exists between BNP and lung diffusion parameters. Resting BNP, DLCO, and DM correlate with peak oxygen consumption ( P < .0001 for all analyses). With exercise, BNP increase is significant (severe LVF 180 ± 49 pg/mL, moderate 68 ± 58, normals 18 ± 12); differently, only in severe LVF, with exercise, DLCO (–1.1 ± 0.7 mL/mm Hg/min, P < .0001) and DM (–6.4 ± 2.8, P < .0006) decrease. One hour after exercise, only in severe LVF, BNP is still higher than at rest, while DLCO, DM, and DM/Vc are lower. Significant correlations are observed between BNP and DM changes during exercise and recovery ( P < .0001) in severe LVF. Conclusions In severe LVF, BNP changes during exercise correlate with simultaneous reductions in DM, suggesting that BNP increase and pulmonary edema formation could be related.

Non-Relapse Mortality (NRM) after Autologous Stem Cell Transplant (ASCT) Is Reduced with Stringent Follow-up Post-Transplant.

Advances in supportive care have reduced early treatment related mortality with ASCT to approximately 1%. ASCT is so well tolerated that it is commonly thought that patients (pts) either relapse or are cured from their disease. However, registry data continues to show that NRM accounts for 25% of treatment failures following ASCT. NRM in this setting is poorly studied and represents a possible area of intervention. We previously reported on NRM at the Cleveland Clinic (ASH 2007: Abstract 1671) in which we reviewed 1573 consecutive autologous transplants performed between 1/92 and 12/05. This analysis included only adult pts receiving peripheral stem cells, single transplants, busulfan based preparative regimens, diagnoses of HL, NHL and MM (n=856). Relapse was the most common cause of death in 303 (79%) pts with NRM occurring in 82 pts (21% of deaths). The most common cause of NRM was pulmonary toxicity in 26 pts, followed by secondary malignancy (19 pts), infection (12 pts), cardiac toxicity (7 pts), other organ failure (7pts) and other causes (11 pts). The majority of NRM from pulmonary toxicity, other organ failure and infection occurred within one year of transplant. Forty-seven patients died within 100 days of transplant – 30 from relapse and 17 from NRM. In an effort to reduce NRM, we targeted pulmonary toxicity as a point of intervention. To identify pts at higher risk for pulmonary toxicity we prospectively followed 137 consecutive pts from 4/05 to 4/06 with monthly phone calls from the BMT nurses using a questionnaire focused to identify pts with symptoms of pulmonary toxicity, and obtained PFTs 1 and 6 months post-ASCT. 12/137 pts had a decrease in DLCO with 7 (58%) of events occurring within one month of transplant, an additional 4 (33%) events within 6 months and one event (9%) at 11 months. HL was the underlying diagnosis in 41% of pts, and prior radiation therapy (XRT) was also identified as a risk factor. Based on this analysis high risk pts were then defined as pts with a decline in DLCO >25% at one month post-ASCT, pts with HL and those with history of prior XRT. High risk pts received 4 and 8 months post-ASCT PFTs. Increased vigilance for the low risk group included phone calls at 3, 6 and 12 months to check for symptoms of pulmonary dysfunction. Patients experiencing a drop in DLCO of >25% at any point in time received a course of steroids and repeat PFT testing. The patient's local oncologist also received a letter which included a copy of CDC vaccination guidelines with recommendations for re-immunization at one year post-ASCT, and a list of signs and symptoms of delayed pulmonary toxicity. To evaluate if changes made to our follow-up protocol impacted on rates of NRM, we identified 149 pts undergoing ASCT from 5/06 to 12/07 (using the same inclusion criteria as the original cohort). Data regarding the original 856 patients was also updated. For the 5/06 to 12/07 study group 127 pts (85%) are alive and 22 pts (15%) have died. Twenty pts (90.9 %) died from relapse and 2 pts (9.1%) died from NRM, both due to pulmonary toxicity. Only two patients died within 100 days of transplant, both due to relapse. There was no NRM within 100 days of transplant. On multivariable analysis of risk factors for NRM for all patients, year of transplant (1/92 to 12/05) emerged as a risk factor for NRM (HR 5.24, P=0.026). Age at transplant (HR 1.26, P=.013), number of prior chemotherapy regimens (HR 1.24, P=.019), prior radiation (HR 1.81, P=.006) and time to platelet engraftment (HR 0.24, P=.001) also emerged as risk factors for NRM. We have adopted more stringent post-ASCT surveillance protocols and while follow-up is short, results suggest that it may be possible to reduce NRM after ASCT.

Bleomycin dose modification in Hodgkin disease (HD) treated with ABVD: Patient characteristics, treatment outcomes, and association with mixed cellularity (MC) histology

18525 Background: Bleomycin used in the ABVD regimen is associated with a risk of pulmonary toxicity (10 - 19%). Pts with early signs of suspected bleomycin toxicity are often treated with modifications of the regimen. We conducted a retrospective study of patients with HD at our institution in whom bleomycin dose was modified or discontinued during their course of therapy with ABVD. Their response to modified therapy and possible predisposing factors were analysed. Methods: IRB approval was obtained for this study. Tumor registry data for adult pts diagnosed with HD between 2004 and 2006 were analysed for age, stage, sex, histology, smoking history, reduction in bleomycin dose and outcomes. Results: 38 pts were diagnosed with HD at our institution during this time period. Histology: NS: n=15(39.4%), MC: n=16(42.1%), NLP: n=2(5.2%), LR: n=2(5.2%). Histology NOS: n=4(10.5%). 8 pts with bleomycin dose modifications were identified. Pt. characteristics : Med.age 46 yrs (28- 64 ), M:F3:5; 7 of 8 were newly diagnosed and one pt had recurrent HDs. Stages: Stg I: n = 1; Stg II: n= 3; Stg III: n = 3, Stage IV: n= 1, B symptoms : n = 3. Histology: MC (n = 6), NS (n = 1). Unk n=1. 4 of 8 pts were ex-smokers. One patient never received bleomycin due to initial poor PFTs. 7 pts had bleomycin discontinued due to symptoms and decrease in DLCO during their treatment. One patient was continued on 50% reduced dose bleomycin for 2 cycles prior to discontinuation of bleomycin. The distribution of the number of patients discontinuing bleomycin by cycle of treatment is as follows: C#2: n=1; C#3: n=2; C#4: n=1; C#5: n=2. The complete response rate was 100% in this group despite bleomycin dose modification. There were no relapses after a median follow up of 18 mos (range: 8- 33). One patient treated for recurrent HD had severe pulmonary toxicity and did not receive any further treatments. All other patients completed their intended cycles of treatment. Conclusions: Despite bleomycin modification in this small series of pts treated initially with ABVD, DFS remains excellent with no noted relapses at this early follow up. Majority of pts requiring dose modifications had MC histology. Further trials are needed to evaluate the role of bleomycin in the ABVD regimen. No significant financial relationships to disclose.

Lower Airway Inflammation Assessed by Induced Sputum in a Cluster of Cases Suggestive of Organic Dust Toxic Syndrome

in a Cluster of Cases Suggestive of Organic Dust Toxic Syndrome R. Castano, J. L. Malo, C. Lemiere, M. Labrecque, A. Cartier; Hopital du Sacre-Coeur de Montreal, Montreal, PQ, CANADA. RATIONALE: To examine pulmonary responses and characterize airway inflammation in workers with respiratory symptoms suggestive of Organic Dust Toxic Syndrome (ODTS). METHODS: We assessed 14 workers of a large factory of sanitary napkins complaining of recurrent work-related cough, shortness of breath, phlegm production and fever with chills. All workers underwent specific inhalation challenges (SIC) for 2 to 4 hours with dust obtained from the floor next to the operating machines. All subjects had measurements of temperature, expiratory flows, white blood cell count (WBC), carbon monoxide diffusing capacity (DLCO) and induced sputum before and after exposure. RESULTS: Only one subject presented symptoms on exposure suggesting extrinsic allergic alveolitis (EAA) with increases in temperature (36.3 to 37.88C) and WBC (5.2 to 10.7 cells per cc) and a decrease in DLCO (23.3 to 18.4). After exposure only one subject had a significant decrease (26%) in forced expiratory volume in one second. In induced sputum 13 subjects had an increase in total cell counts (mean 55.3 10 c/ml; range 8.2-113.4) and 12 in neutrophils (mean 39%; range 20-92%). CONCLUSIONS: We have thus described workers with features of ODTS, EAA and asthma. We hypothesize that these conditions may be considered one syndrome with a wide spectrum of severity ranging from a less severe condition (ODTS) in one end of the spectrum to a more severe disease in the other (EAA). Results also support the use of induced sputum in the investigation of ODTS. The etiology of this syndrome in our workers is still unknown. Funding: Universite de Montreal