Lung Function Predicts Outcome in Children With Obstructive Lung Disease After Hematopoietic Stem Cell Transplantation.

Obstructive lung disease (OLD) that develops after hematopoietic stem cell transplantation (HSCT) has a significant impact on morbidity and mortality. We investigated the role of pulmonary function tests (PFTs) in the prediction of prognosis of OLD in children who have undergone HSCT. We retrospectively reviewed 538 patients who underwent allogenic HSCT in the Department of Pediatrics, Seoul St. Mary's Hospital, South Korea, from April 2009 to July 2017. OLD was identified on PFTs or chest computed tomography scans obtained from 3 months after HSCT onwards. OLD developed after HSCT in 46 patients (28 male individuals, median age: 11.2 y). The group that developed OLD with an unfavorable prognosis (n=23) had a lower forced vital capacity (FVC) (% of predicted, 78.53±24.00 vs. 97.71±16.96, P=0.01), forced expiratory volume in 1 second (FEV1) (% of predicted, 52.54±31.77 vs. 84.44±18.59, P=0.00), FEV1/FVC (%, 59.28±18.68 vs. 79.94±9.77, P=0.00), and forced expiratory flow at 25% to 75% of forced vital capacity (FEF25-75) (% of predicted, 30.95±39.92 vs. 57.82±25.71, P=0.00) at diagnosis than the group that developed OLD with a favorable prognosis (n=23). The group that developed OLD with an unfavorable prognosis had significant reductions in FVC, FEV1, FEV1/FVC, and FEF25-75 at 2 years after diagnosis. Children who develop OLD with an unfavorable prognosis after HSCT already have poor lung function at the time of diagnosis. Additional treatment should be considered in patients who develop OLD after HSCT according to their PFTs at diagnosis.

[Early outcomes following lung transplantation in patients aged 65 years and older]. / Résultats précoces de la transplantation pulmonaire chez les patients âgés de 65 ans et plus.

INTRODUCTION: The number of lung transplantations performed is increasing worldwide. With an improved experience and outcomes, the age of the recipient on its own has ceased to be an absolute contra-indication. We report our first experience with lung transplantation in patients aged 65 years or older. METHODS: From January 2014 to March 2019, the files of patients aged 65 years or older undergoing lung transplantation were retrospectively reviewed. RESULTS: During the study period, 241 patients underwent lung transplantation in Bichat hospital (Paris, France), including 25 recipients aged 65 years or older. Underlying diagnoses were interstitial (72%) and obstructive (28%) disease. The rate of single lung transplantation was 80%. Sixteen patients required ECMO assistance during the procedure. Early complications were mostly grade III primary graft dysfunction (12%) and cellular rejection (20%). Overall one-year survival rate was 76%. CONCLUSION: After a careful selection of the recipients, the early results of our retrospective single center series are encouraging. We continue to consider lung transplantation in rigorously selected recipients of aged 65 years and more.

Outcomes of lung disease-associated pulmonary hypertension and impact of elevated pulmonary vascular resistance.

BACKGROUND: The clinical characteristics, hemodynamic changes and outcomes of lung disease-associated pulmonary hypertension (LD-PH) are poorly defined. METHODS: A prospective cohort of PH patients undergoing initial hemodynamic assessment was collected, from which 51 patients with LD-PH were identified. Baseline characteristics and long-term survival were compared with 83 patients with idiopathic pulmonary arterial hypertension (iPAH). RESULTS: Mean age (±standard deviation) of LD-PH patients was 64 ±â€¯10 years, 30% were female and 78% were New York Heart Association class III-IV. The LD-PH group was older than the iPAH group (64 ±â€¯10 vs 56 ±â€¯18 years, respectively, P = 0.003) with a lower percentage of women (30% vs 70%, P = 0.007). LD-PH patients had smaller right ventricular sizes (P = 0.02) and less tricuspid regurgitation (P = 0.03) by echocardiogram, and lower mean pulmonary arterial pressures (mPAP) (P = 0.01) and pulmonary vascular resistance (PVR) (P = 0.001) at catheterization. Despite these findings, mortality was equally high in both groups (P = 0.16). 5-year survival was lower in patients with interstitial lung disease compared to those with obstructive pulmonary disease (P = 0.05). Among the LD-PH population, those with mild to moderately elevated mPAP and those with PVR <7 Wood units demonstrated significantly improved survival (P = 0.04 and P = 0.001, respectively). Vasoreactivity was not associated with improved survival (P = 0.64). A PVR ≥7 Wood units was associated with increased risk of mortality (hazard ratio (95% confidence interval), 3.59 (1.27-10.19), P = 0.02). CONCLUSIONS: Despite less severe PH and less right heart sequelae, LD-PH has an equally poor clinical outcome when compared to iPAH. A PVR ≥7 Wood units in LD-PH patients was associated with 3-fold higher mortality.

External Validation and Recalculation of the CODEX Index in COPD Patients. A 3CIAplus Cohort Study.

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25-75% 426-1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up.

Power and sample size for dose-finding studies with survival endpoints under model uncertainty.

Multiple comparison procedures combined with modeling techniques (MCP-Mod) (Bretz et al., 2005) is an efficient and robust statistical methodology for the model-based design and analysis of dose-finding studies with an unknown dose-response model. With this approach, multiple comparison methods are used to identify statistically significant contrasts corresponding to a set of candidate dose-response models, and the best model is then used to estimate the target dose. Power and sample size calculations for this methodology require knowledge of the covariance matrix for the estimators of the (placebo-adjusted) mean responses among the dose groups. In this article, we consider survival endpoints and derive an analytic form of the covariance matrix for the estimators of the log hazard ratios as a function of the total number of events in the study. We then use this closed-form expression of the covariance matrix to derive the power and sample size formulas. We discuss practical considerations in the application of these formulas. In addition, we provide an illustration with a motivating example on chronic obstructive pulmonary disease. Finally, we demonstrate through simulation studies that the proposed formulas are accurate enough for practical use.

Rate control and clinical outcomes in patients with atrial fibrillation and obstructive lung disease.

BACKGROUND: Rate-control medications are considered first-line treatment for patients with atrial fibrillation (AF). However, obstructive lung disease (OLD), a condition prevalent in those with AF, often makes it difficult to use those medications because of the lack of studies on new-onset AF in patients with OLD. OBJECTIVE: The purpose of this study was to investigate clinical outcomes after administration of each class of rate-control medication in patients with concomitant AF and OLD (AF-OLD). METHODS: This study used the entire database provided by the National Health Insurance Service from 2002 to 2015. Risk of all-cause mortality was compared between use of calcium channel blocker (CCB) and use of other drug classes in AF-OLD patients using Cox regression analyses after propensity score matching. RESULTS: Among the 13,111 patients, the number of AF-OLD patients treated with a CCB, cardioselective ß-blocker (BB), nonselective BB, and digoxin was 2482, 2379, 2255, and 5995, respectively. The risk of mortality was lower with use of selective BB (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94; P = .002) and nonselective BB (HR 0.85; 95% CI 0.77-0.95; P = .003) compared to use of CCBs. Digoxin use was related with worse survival, with marginal statistical significance (HR 1.09; 95% CI 1.00-1.18; P = .053). CONCLUSION: Among patients with AF-OLD, rate-control treatment using selective and nonselective BB was associated with a significant reduction in mortality compared with CCB use. Further prospective randomized trials are required to confirm these findings.

Harmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.

Difference in Mortality Risk in Elderly People with Bronchial Obstruction Diagnosed Using a Fixed Cutoff or the Lower Limit of Normal of the FEV1/FVC Ratio.

BACKGROUND: Whether a fixed cutoff or the lower limit of normal of the FEV1/FVC ratio should be used to diagnose bronchial obstruction is still a matter of debate. This issue is particularly important for elderly people. OBJECTIVES: We used equations applicable up to 90 years of age to evaluate the mortality of elderly people diagnosed with bronchial obstruction using either a fixed cutoff of 0.7 or the lower limit of normal (LLN). METHODS: Participants in the SaRA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study were grouped as follows: FEV1/FVC ≥0.7 and ≥ LLN (n = 535: F-/L-), FEV1/FVC <0.7 but ≥ LLN (n = 118: F+/L-), and FEV1/FVC <0.7 and < LLN (n = 229: F+/L+). We estimated the mortality risk in the three groups over 15 years of follow-up. RESULTS: The mean age was 73 years (58% men). The hazard ratio (HR) for mortality was 1.427 (95% CI: 1.09-1.868) in the F+/L- group and 2.143 (95% CI: 1.13-1.995) in the F+/L+ group. After adjustment for potential confounders, we found no increased mortality in the F+/L- group (HR: 1.007, 95% CI: 0.755-1.342), while the HR in the F+/L+ group was still sizeable (1.474, 95% CI: 1.136-1.911). CONCLUSIONS: As expected, using a fixed cutoff translates in a larger number of people to be classified as having bronchial obstruction. In our sample the increased mortality in the F+/L- group is due to the confounding effect of age and sex. Our study lends support to the use of LLN in elderly people.

Impact of restrictive lung disorder on cardiovascular mortality in a general population: The Yamagata (Takahata) study.

BACKGROUND: Obstructive lung disorder (OLD) is known to be associated with cardiovascular disease. However, the impact of restrictive lung disorder (RLD) on cardiovascular mortality has not been fully investigated in the apparently healthy general population. OBJECTIVES: To clarify whether RLD is associated with cardiovascular mortality in the general population. METHODS AND RESULTS: This community-based cohort study included 3247 subjects who participated in an annual health check in Takahata. We performed spirometry in registered subjects and found that 194 (6%) had RLD, 262 (8%) had OLD, and 73 (2%) had RLD and OLD (Mixed). During a 10-year follow-up, there were 210 deaths, including 57 cardiovascular deaths. Cardiovascular mortality of subjects with RLD was significantly higher than that of subjects with normal lung function. Although the subjects with RLD were younger, comprised fewer smokers, and were more likely to be female than those with OLD, cardiovascular mortality of subjects with RLD was comparable to that of subjects with OLD. Subjects with RLD had a higher prevalence of atrial fibrillation (AF) than those with OLD, and the prevalence of AF was increased with advanced severity of RLD. Multivariate Cox proportional hazard analysis revealed that RLD was an independent predictor of cardiovascular death (hazard ratio 2.61, 95% confidence interval, 1.22-5.21) after adjustment for confounders, but OLD was not. The net reclassification improvement and integrated discrimination improvement were significantly increased by the addition of RLD to conventional cardiovascular risk factors. CONCLUSION: The presence of RLD was associated with cardiovascular mortality in the general population.

Survival Benefit of Lung Transplantation in the Modern Era of Lung Allocation.

RATIONALE: Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood. OBJECTIVES: To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation. METHODS: Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined. MEASUREMENTS AND MAIN RESULTS: Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P < 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40. CONCLUSIONS: A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy.

Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.

In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti-tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients.

Trends in hospital admissions for obstructive lung disease from 2000 to 2010 in Portugal.

The burden of hospitalisations for obstructive lung diseases (OLD) has not been sufficiently studied. We aimed to characterise the hospitalisations for OLD from 2000 to 2010 in all Portuguese public hospitals. We analysed hospital discharges with a diagnosis of OLD regarding the patients' gender, age, residence and comorbidities. Of the 120 399 hospital admissions with a principal diagnosis of OLD, COPD (ICD-9-CM 491.x, 492.x, 496) was responsible for 81%. The change in patients discharged with OLD as a principal diagnosis was only 1% from 2000 to 2010 and did not change for COPD. Hospital admissions and deaths for COPD and other OLD increased with age and were more common in men than women. In-hospital mortality for COPD decreased 34.1% from 2000 to 2010, while the median length of stay was fairly constant at 8 days. Respiratory failure, insufficiency and/or arrest, and pneumonia, are the principal diagnoses often associated with COPD. When both pneumonia and COPD were diagnosed there was an increasing trend to classify pneumonia as the principal diagnosis (64.4%-72.9%), a sign that may lead to underestimation of COPD hospitalisations. In summary, a considerable decrease in in-hospital COPD mortality was observed while hospital admissions and the length of stay did not change substantially. These results suggest that better healthcare or other factors may be counteracting the expected increase of the burden of COPD.

Exercise Parameters and Risk of Coronary Artery Disease and Mortality Among Patients Who Use Pulmonary Medications: The FIT Project.

BACKGROUND: In the general population, the exercise treadmill testing variables of lower resting heart rate, higher peak heart rate, and greater fitness have favorable prognosis for mortality. Patients with obstructive lung disease have increased mortality risk. Furthermore, some pulmonary medications (ie, beta2-agonists) can influence heart rate. We determined whether exercise treadmill test parameters carry the same prognostic value in patients who are using versus not using pulmonary medications. METHODS: We analyzed data on 69,855 patients (mean age, 55 years) who completed a clinically indicated exercise treadmill test. Patients were defined as having "lung disease" if they were taking medications routinely used to treat obstructive lung disease (n = 6145, 9%). International Classification of Diseases, 9th Revision codes regarding the type of lung disease were not available. Multivariate-adjusted Cox models were used to determine the risk of mortality, major adverse cardiac events, and myocardial infarction over a mean of 11 years follow-up. RESULTS: Higher resting heart rate was associated with increased mortality risk, and higher peak heart rate and fitness were associated with decreased risk. No significant interaction for lung disease status was seen for the heart rate variables, but a slightly stronger protective effect was observed for higher fitness among patients with lung disease (P interaction = .032). The results were similar for major adverse cardiac events and myocardial infarction. CONCLUSIONS: Heart rate parameters achieved on exercise treadmill tests are equally prognostic among patients using versus not using pulmonary medications. Higher fitness was associated with improved clinical outcomes for both; however, the relative benefit of fitness on survival was even greater in patients using pulmonary medications compared with those not using them.

Lung Infarction Following Pulmonary Embolism: A Comparative Study on Clinical Conditions and CT Findings to Identify Predisposing Factors.

PURPOSE: The aim of this study was to identify factors predisposing to lung infarction in patients with pulmonary embolism (PE). MATERIALS AND METHODS: We performed a retrospective analysis on 154 patients with the final diagnosis of PE being examined between January 2009 and December 2012 by means of a Toshiba Aquilion 64 CT scanner. The severity of clinical symptoms was defined by means of a clinical index with 4 classes. The pulmonary clot load was quantified using a modified severity index of PE as proposed by Miller. We correlated several potential predictors of pulmonary infarction such as demographic data, pulmonary clot burden, distance of total vascular obstruction and pleura, the presence of cardiac congestion, signs of chronic bronchitis or emphysema with the occurrence of pulmonary infarction. RESULTS: Computed tomography revealed 78 areas of pulmonary infarction in 45/154 (29.2 %) patients. The presence of infarction was significantly higher in the right lung than in the left lung (p < 0.001). We found no correlation between pulmonary infarction and the presence of accompanying malignant diseases (r = -0.069), signs of chronic bronchitis (r = -0.109), cardiac congestion (r = -0.076), the quantified clot burden score (r = 0.176), and the severity of symptoms (r = -0.024). Only a very weak negative correlation between the presence of infarction and age (r = -0.199) was seen. However, we could demonstrate a moderate negative correlation between the distance of total vascular occlusion and the occurrence of infarction (r = -0.504). CONCLUSION: Neither cardiac congestion nor the degree of pulmonary vascular obstruction are main factors predisposing to pulmonary infarction in patients with PE. It seems that a peripheral total vascular obstruction more often results in infarction than even massive central clot burden.

What happens to patients with COPD with long-term oxygen treatment who receive mechanical ventilation for COPD exacerbation? A 1-year retrospective follow-up study.

We performed a retrospective cohort study of patients with chronic obstructive lung disease (COPD) on long-term oxygen treatment (LTOT) who received invasive mechanical ventilation for COPD exacerbation. Of the 4791 patients, 23% died in the hospital, and 45% died in the subsequent 12 months. 67% of patients were readmitted at least once in the subsequent 12 months, and 26.8% were discharged to a nursing home or skilled nursing facility within 30 days. We conclude that these patients have high mortality rates, both in-hospital and in the 12 months postdischarge. If patients survive, many will be readmitted to the hospital and discharged to nursing home. These potential outcomes may support informed critical care decision making and more preference congruent care.

Lung function, 25-hydroxyvitamin D concentrations and mortality in US adults.

OBJECTIVE: To explore the associations between serum concentrations of vitamin D (25(OH)D) and all-cause mortality among US adults defined by lung function (LF) status, particularly among adults with obstructive LF (OLF). METHODS: Data from 10,795 adults aged 20-79 years (685 with restrictive LF (RLF) and 1309 with OLF) who participated in the Third National Health and Nutrition Examination Survey (1988-1994), had a spirometric examination, and were followed through 2006 were included. RESULTS: During 14.2 years of follow-up, 1792 participants died. Mean adjusted concentrations of 25(OH)D were 75.0 nmol/l (s.e. 0.7) for adults with normal LF (NLF), 70.4 nmol/l (s.e. 1.8) for adults with RLF, 75.5 nmol/l (s.e. 1.5) for adults with mild obstruction and 71.0 nmol/l (s.e. 1.9) among adults with moderate or worse obstruction (P=0.030). After adjustment for sociodemographic factors, lifestyle factors, clinical variables and prevalent chronic conditions, a concentration of <25 nmol/l compared with ⩾ 75 nmol//l was associated with mortality only among adults with NLF (hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.03, 3.00). Among participants with OLF, adjusted HRs were 0.65 (95% CI 0.29, 1.48), 1.21 (95% CI 0.89, 1.66) and 0.97 (95% CI 0.78, 1.19) among those with concentrations <25, 25-<50 and 50-<75 nmol/l, respectively. CONCLUSIONS: Baseline concentrations of 25(OH)D did not significantly predict mortality among US adults with impaired LF.

Deaths of obstructive lung disease in the Yangpu district of Shanghai from 2003 through 2011: a multiple cause analysis.

BACKGROUND: Obstructive lung disease (OLD, chronic obstructive pulmonary disease or asthma) is an important cause of death in older people. There has been no exhaustive population-based mortality study of this subject in Shanghai. The objective of this study was to use a multiple cause of death methodology in the analysis of OLD mortality trends in the Yangpu district of Shanghai, from 2003 through 2011. METHODS: We analyzed death data from the Shanghai Yangpu District Center for Disease Control and Prevention for Medical Cause of Death database, selecting all death certificates for individuals 40 years or older on which OLD was listed as a cause of death. RESULTS: From 2003 to 2011, there were 8 775 deaths with OLD listed, of which 6 005 (68%) were identified as the underlying cause of death. For the entire period, a significantly decreasing trend of age standardized rates of death from OLD was observed in men (-6.2% per year) and in women (-5.7% per year), similar trends were observed in deaths with OLD. The mean annual rates of deaths from OLD per 100 000 were 161.2 for men and 80.8 for women from 2003 to 2011. While, as the underlying cause of death, the main associated causes of death were as follows: cardiovascular diseases (70.7%), cerebrovascular diseases (13.3%), diabetes (8.6%), and cancer (4.3%). The associated causes and the principal overall underlying causes of death were cardiovascular diseases (37.0%), cancer (30.3%), and cerebrovascular disease (15.3%). A significant seasonal variation, with the highest frequency in winter, occurred in deaths identified with underlying causes of chronic bronchitis, other obstructive pulmonary diseases, and asthma. CONCLUSIONS: Multiple cause mortality analysis provides a more accurate picture than underlying cause of total mortality attributed on death certificates to OLD. The major comorbidities associated with OLD were cardiovascular disease, cancer, and cerebrovascular disease. From 2003 to 2011, the mortality rate from OLD decreased substantially in the Yangpu district of Shanghai.

Lung function and gas exchange in Eisenmenger syndrome and their impact on exercise capacity and survival.

BACKGROUND: Eisenmenger physiology may contribute to abnormal pulmonary mechanics and gas exchange and thus impaired functional capacity. We explored the relationship between lung function and gas exchange parameters with exercise capacity and survival. METHODS: Stable adult patients with Eisenmenger syndrome (N=32) were prospectively studied using spirometry, lung volumes, diffusion capacity, and blood gas analysis, as well as same day measurement of 6-minute walk distance and cardiopulmonary maximal treadmill exercise. Patients were followed prospectively to determine survival (7.4 ± 0.5 years). Abnormalities were identified and appropriate comparisons were made between affected and unaffected individuals between respiratory mechanics, exercise function, and survival. RESULTS: Obstruction (FEV1/FVC ratio <0.70) was found in 13 patients (41%), who were older but not otherwise different. Restriction was uncommon. Diffusion transfer coefficient, which was <80% in half the patients, correlated with exercise duration (r=0.542, P=0.005), and was worse in non-survivors (N=6). Nearly all patients had a compensated respiratory alkalosis (PaCO2 32 ± 4.4 mm Hg). PaCO2 was less reduced in older patients (r=0.438, P=0.022), and correlated independently with exercise duration (R=-0.463, P=0.03), yet PaO2, not PaCO2, was associated with survival. CONCLUSIONS: Eisenmenger patients show evidence of obstructive lung disease, diffusion abnormalities, and hypocapnia; likely from hyperventilation. Understanding expected lung mechanics and gas exchange may facilitate more appropriate clinical management.