Transitioning from hospital to home with non-invasive ventilation: who benefits? Results of a cohort study.

BACKGROUND: Non-invasive ventilation (NIV) is effective in a variety of acute respiratory illnesses in hospitalised patients. Home NIV is effective for stable patients with hypercapnia due to neuromuscular or chronic pulmonary disease. However, there are little data to guide which patients may benefit from NIV immediately following hospitalisation with hypercapnia. OBJECTIVE: To evaluate outcomes of patients with daytime hypercapnia at the end of an acute hospital admission. DESIGN: Retrospective cohort study. PARTICIPANTS: Entry into the cohort was by querying the hospital electronic medical system for consultations regarding NIV after discharge. Cases received NIV and controls did not. We extracted data on demographics, ICD-9 diagnoses and medications coded at admission, blood gas measurements and dates of discharge, first readmission and death. INTERVENTION: None. MAIN MEASUREMENT: Time from hospital discharge to mortality or readmission. KEY RESULTS: We identified 585 cases and 53 controls who survived to discharge at the index admission. Cases and controls were broadly similar in age and Charlson Comorbidity Index. In the whole cohort, cases treated with home NIV were at increased risk of death compared with controls (HR 1.88 95% CI 1.17 to 3.03). In multivariate Cox regression for all-cause mortality, poor prognostic factors were increasing age (HR 1.03 per year, 95% CI 1.02 to 1.04), cardiac failure (HR 1.31, 95% CI 1.01 to 1.67) and failure to attend NIV follow-up (HR 2.33, 95% CI 1.33 to 4.10). In contrast, chronic respiratory disease was associated with improved prognosis (HR 0.77, 95% CI 0.61 to 0.97) as was sleep apnoea (HR 0.44, 95% CI 0.23 to 0.83). Cases did not have different time-to-readmission compared with controls (HR 1.42 95% CI 0.99 to 2.02). CONCLUSION: Transitioning to home NIV after a hypercapnic hospitalisation may be useful in younger, co-operative patients with chronic respiratory disease. For older patients or those with cardiac failure, home NIV may not be beneficial and may potentially be harmful.

Step oximetry test: a validation study.

INTRODUCTION: Step climbing is a potentially useful modality for testing exercise capacity. However, there are significant variations between test protocols and lack of consistent validation against gold standard cycle ergometry cardiopulmonary exercise testing (CPET). The purpose of the study was to validate a novel technique of exercise testing using a dedicated device. METHODS: We built a step oximetry device from an adapted aerobics step and pulse oximeter connected to a computer. Subjects performed lung function tests, a standard incremental cycle CPET and also a CPET while stepping on and off the step oximetry device to maximal exertion. Data from the step oximetry device were processed and correlated with standard measurements of pulmonary function and cycle CPET. RESULTS: We recruited 89 subjects (57 years, 50 men). Oxygen uptake (VO2) was 0.9 mL/kg/min (95% CI -3.6 to 5.4) higher in the step test compared with the gold standard cycle CPET, p<0.001. VO2 in the two techniques was highly correlated (R=0.87, p<0.001). Work rate during stair climbing showed the best correlation with VO2 (R=0.69, p<0.0001). Desaturation during step climbing correlated negatively with diffusion capacity for carbon monoxide (r=-0.43, p<0.005). No adverse events occurred. CONCLUSIONS: The step oximetry test was a maximal test of exertion in the subjects studied, achieving slightly higher VO2 than during the standard test. The test was safe to perform and well tolerated by the patients. Parameters derived from the step oximetry device correlated well with gold standard measurements. The step oximetry test could become a useful and standardisable exercise test for clinical settings where advanced testing is not available or appropriate.

Tacrolimus Levels Are Not Associated with Risk of Malignancy in Lung Transplant Recipients.

BACKGROUND Lung transplant (LTx) recipients suffer from high rates of malignancy. Exposure to immunosuppressive medication such as tacrolimus has been proposed as a risk factor for tumorigenesis. We hypothesized that chronically high levels of tacrolimus would be associated with risk of malignancy. MATERIAL AND METHODS The study was performed in a transplant center in Israel, with a nested case-control design. Cases were LTx recipients who were diagnosed with any solid or hematological malignancy except non-melanoma skin cancer. Controls were tumor-free during their entire follow-up after LTx and had at least the same follow-up time as their matched case. Controls were matched to cases by age and type of transplant received (single/double). Tacrolimus levels were extracted and analyzed for median drug level and also integrated over time (area under the curve - AUC-tacrolimus). RESULTS We reviewed 412 LTx recipients in our registry. Thirty-nine cases of malignancy were diagnosed and 160 controls were matched, giving a crude tumor incidence rate of 26/100 000/year. Lung cancers were the commonest diagnosis. Cases and controls were well matched by age, smoking status, and LTx type. Median tacrolimus levels were 11.0 ng/ml and 11.3 ng/ml in cases and controls, respectively (p=0.88). The median log (AUC-tacrolimus) was 9.4 in the cases and 9.5 in the controls (p=0.59). CONCLUSIONS In this nested case-control study, exposure to tacrolimus was similar in tumor cases and non-tumor controls. These data, based on a cohort with modest size, suggest either that tumorigenesis in LTx recipients is unrelated to tacrolimus exposure or that levels in these patients are above an unknown threshold at which the dose-response effect is saturated.

The Prognostic Role of Ventilatory Inefficiency and Exercise Capacity in Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal interstitial lung disease associated with poor prognosis and limited effective treatment options. Reliable predictors of outcome in daily clinical practice are needed to determine high-risk patients for urgent lung transplantation referral. This study aimed to identify practical prognostic predictors of mortality using cardiopulmonary exercise testing (CPET) in IPF subjects. METHODS: Thirty-four subjects with IPF (22 men and 12 women), median age 68 (range 50-81) y were prospectively studied. At baseline, all subjects were assessed with CPET and were followed up for 40 months from baseline. Receiver operating characteristic curve analysis was conducted to determine cut-off points of CPET variables for mortality, Cox regression analysis for survival using a log-rank test, and hazard ratio for death using a Wald test. RESULTS: Peak work rate <62 watts (P = .005), peak V̇O2 ≤13.8 mL/kg/min (P = .031), tidal volume reserve ≤0.48 L/breath (P = .010), minute ventilation to carbon dioxide (V̇E)/V̇CO2 ) ratio at the anaerobic threshold >34 (P = .02), and V̇E)/V̇O2 nadir >34 (P = .002) were detected as cut-off points associated with mortality. Non-survivor subjects were characterized by higher dyspnea levels, the presence of pulmonary hypertension assessed by echocardiography, pronounced inefficient ventilatory pattern, lower exercise capacity, and more severe desaturation during physical exertion. By the end of the study, 11 subjects (7 women and 4 men) died. Overall mean survival was 60%, 33.7 months (95% CI 30.2-37.2). CONCLUSIONS: This study provides simple, practical, and novel cut-off points for CPET as predictors of prognosis to identify high-risk IPF subjects. Impairment in exercise capacity and abnormal ventilatory responses during CPET were associated with poorer survival in IPF subjects. The findings suggest considering the use of CPET for IPF risk stratification and prediction of prognosis. (ClinicalTrials.gov registration NCT01499745.).

Physiological Profile and Limitations in Exercise in Idiopathic Pulmonary Fibrosis.

PURPOSE: This study aimed to describe the physiological profile and limiting factors during exercise among patients with idiopathic pulmonary fibrosis. METHODS: A descriptive study involving 34 patients with idiopathic pulmonary fibrosis (22 men) aged 68 ± 8 years was conducted. All patients completed a pulmonary function test, cardiopulmonary exercise test, Doppler echocardiography, 6-minute walk test, and modified Medical Research Council dyspnea evaluation. RESULTS: Approximately 38% of patients (range, 15%-71%) presented with coexisting comorbidities including pulmonary hypertension and emphysema. Modified Medical Research Council grades 0-2 and 3-4 were assigned to 68% and 32% of patients, respectively. Median values for forced vital capacity and diffusion capacity for carbon monoxide percent (%) predicted were 68 (95% CI, 63-76) and 51 (95% CI, 46-55), respectively. Left ventricular systolic function was normal. Aerobic capacity ((Equation is included in full-text article.)O2peak = 13.4 mL/kg/min [95% CI, 12.6-14.9]; 62% predicted [95% CI, 56-67]) was moderately reduced with the presence of abnormalities in pulmonary gas exchange and desaturation, circulatory impairments, inefficient ventilation, and skeletal muscle dysfunction. Functional capacity was normal (6-minute walk test distance = 505 m [95% CI, 435-522]; 99% predicted [95% CI, 91-108]). CONCLUSIONS: The physiological profile demonstrated the presence of comorbidities in approximately 38% of patients with idiopathic pulmonary fibrosis and a moderate level of dyspnea. Resting cardiopulmonary function showed moderate pulmonary restriction and severe impairments in diffusion capacity with normal left ventricular systolic function. Multifactorial limitations for a moderately diminished aerobic capacity were revealed during the cardiopulmonary exercise test, although functional capacity was normal. These results emphasize the significance of a meticulous evaluation, including the cardiopulmonary exercise test for an accurate exercise tolerance evaluation, to aid in the diagnosis and prognosis and for developing effective targeted treatments.

Short-Term Improvement in Physical Activity and Body Composition After Supervised Exercise Training Program in Idiopathic Pulmonary Fibrosis.

OBJECTIVE: To examine the effect of participating in a 12-week supervised exercise training (ET) program on physical activity and body composition in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: Randomized controlled trial assessing physical activity and body composition at baseline, after 12-week intervention, and at 11 months follow-up. SETTING: Outpatient hospital. PARTICIPANTS: Patients with IPF (N=34; mean age, 68±8y) recruited for this study; 32 patients completed the 12-week intervention (ET group: n=15; control group: n=17) and 28 patients (14 in each group) reassessed at 11-month follow-up from baseline. INTERVENTIONS: Participation in a 12-week supervised ET program or regular medical treatment. MAIN OUTCOME MEASURES: Changes in physical activity levels as measured by the International Physical Activity Questionnaire. RESULTS: After the 12-week intervention, physical activity levels were significantly increased in the ET group whereas the control group showed a trend toward deterioration (median difference between the groups, 2164MET-min/wk [interquartile range, 1576MET-min/wk]; MET = metabolic equivalent; P<.001). Body composition was also significantly improved in the ET group, whereas the control group showed an opposite trend. At 11-month follow-up, no significant differences were observed between the 2 groups in all variables. The ET group lost most of the achieved improvements in the outcomes and returned to near baseline levels, whereas the control group showed a trend toward worsened outcomes. CONCLUSIONS: Physical activity and body composition in patients with IPF were improved after a 12-week supervised ET program, although the benefits were not sustained at 11-month follow-up. These results may support the efficacy of participation in supervised ET to improve physical activity and body composition in patients with IPF; however, maintenance strategies are warranted to preserve the improved outcomes.

Exercise training in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic devastating interstitial lung disease associated with exercise intolerance, dyspnea, hypoxemia, diminished quality of life and poor prognosis. A growing body of evidence with respect to short-term effects of exercise training has demonstrated clinical benefits in IPF patients. A recent systematic review showed significant improvements in 6-min walking distance, peak aerobic capacity, reduced dyspnea and improved quality of life. However, aspects of training programs, maintenance and predictors of improvement and the impact on prognosis need to be further explored. The aim of this paper was to comprehensively review the existing scientific literature regarding exercise training in patients with IPF and identify important gaps that should be studied in the future.

Long-term effects of a 12-week exercise training program on clinical outcomes in idiopathic pulmonary fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, lung disease, with few therapeutic options. Data are limited with respect to the long-term effect of exercise training (ET) in IPF. This study sought to evaluate the long-term effects of a 12-week ET program on clinical outcomes in IPF patients. METHODS: Thirty-four IPF patients were randomly allocated to ET or control groups. ET group participated in a 12-week supervised exercise program, while the control group continued with regular medical treatment alone. Exercise capacity, 30 s-chair-stand test for leg strength, dyspnea, and Saint George's Respiratory Questionnaire (SGRQ) for quality of life (QOL) were assessed at baseline and re-evaluated at 11 months from baseline. In addition, at 30-month time point from baseline, the impact of the 12-week intervention was analyzed with respect to survival and cardio-respiratory-related hospitalizations. RESULTS: Thirty-two patients completed the 12-week intervention and 28 patients (14 in each group) were re-evaluated. At 11-month follow-up, no significant differences between the groups and time effect were demonstrated for most outcomes. ET group showed preserved values at the baseline level while the control group showed a trend of deterioration. Only the 30 s-chair-stand test (mean difference 3 stands, p = 0.01) and SGRQ (mean difference -6 units, p = 0.037) were significantly different between the groups. At 30 months, the survival analysis showed three deaths, eight hospitalizations occurred in the control group versus one death, one lung transplantation and seven hospitalizations in the ET group, with no significant differences between groups. CONCLUSIONS: At 11-month follow-up, the 12-week ET program showed clinical outcomes were preserved at baseline levels with some maintenance of improvements in leg strength and QOL in the ET group. The control group showed a trend of deterioration in the outcomes. At 30 months, the 12-week ET program did not show benefits in prognosis although the study was underpowered to detect such differences. We suggest including ET as a long-term continued treatment and as a core component of pulmonary rehabilitation programs for IPF patients.

Limitations in exercise and functional capacity in long-term postpneumonectomy patients.

INTRODUCTION: Pneumonectomy results in impairments of pulmonary function and exercise intolerance associated with respiratory limitations. However, exercise capacity and functional capacity are less known at long-term followup. The aims of this study were to assess exercise tolerance and functional capacity among long-term postpneumonectomy patients and to identify the limiting factors in exercise related to comorbidities and which lung was involved. METHODS: Seventeen postpneumonectomy patients aged 59 ± 13 years and 5.5 ± 4.2 years postoperation were prospectively studied. Pulmonary function tests (PFTs), cardiopulmonary exercise test (CPET), Doppler-echocardiography, 6-minute walk test (6MWT) distance, and "senior fitness tests" (SFTs) were conducted with all patients. RESULTS: Exercise capacity and PFT were diminished ((Equation is included in full-text article.)O2 peak; 11.5 ± 3.3 mL·kg·min, 48 ± 17% predicted, forced vital capacity % predicted; 55 ± 13, FEV1% predicted; 46 ± 14, respectively). Most patients presented with low exercise cardiovascular parameters and normal breathing reserve (17 ± 12 L) during CPET. No significant differences were shown between right and left pneumonectomy and comorbidities related to exercise limitations (χ= 1.96, P = .376). Functional capacity in walking and SFTs were near normal (6MWT distance; 490 ± 15 m, 89 ± 25% predicted). Echocardiography showed normal left ventricle systolic function (ejection fraction, 60 ± 4%) with mildly elevated systolic pulmonary arterial pressure (38 ± 12 mm Hg). CONCLUSIONS: Long-term postpneumonectomy patients demonstrated decreased exercise capacity, limited primarily by the cardiovascular system regardless of lung resection side or comorbidities, although tests of functional capacity were near normal. Most patients can maintain near normal life in activities of daily living, but the long-term cardiopulmonary exercise function should be considered for meticulous evaluation and clinical care to preserve physiological reserves.

Exercise training-based pulmonary rehabilitation program is clinically beneficial for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, interstitial lung disease, with few therapeutic options. IPF is characterized by pulmonary restriction, dyspnea, hypoxemia, exercise intolerance and poor quality of life (QOL). OBJECTIVES: We aimed to examine the effect of exercise training (ET) on clinical outcomes in IPF patients. METHODS: A randomized controlled study included thirty-two IPF patients (aged 68 ± 8 years) who were allocated either to the ET group (n = 15), participating in a 12-week, twice-weekly 60-min supervised ET-based pulmonary rehabilitation program, or to a control group (n = 17) continuing with regular medical treatment alone. Cardiopulmonary exercise test, 6-min walking distance (6MWD) test, 30-second chair-stand test, pulmonary function tests, dyspnea and QOL were assessed at baseline and at the end of the 12-week intervention. RESULTS: Significant differences were observed between the ET and the control groups in raw mean deltas (Δ = post- - pre-intervention): Δ6MWD, 81 m, p < 0.001; ΔVO2 peak, 2.6 ml/kg/min, p = 0.002; Δwork rate, 22 W, p < 0.001; Δanaerobic threshold, 3.1 ml/kg/min, p < 0.001, and ΔFVC % predicted, 6%, p = 0.038. Dyspnea, QOL and 30-second chair-stand were also improved significantly following the program. CONCLUSIONS: ET improves exercise tolerance, functional capacity, pulmonary function, dyspnea and QOL in patients with IPF, suggesting a short-term treatment efficacy for clinical improvement, and should be considered the standard care for IPF.

Step climbing capacity in patients with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps. OBJECTIVES: To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test. METHODS: We built a step oximetry system from an 'aerobics' step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO(2) and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance, desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record. RESULTS: Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p < 0.001). There was a good correlation between exercise performance on the step and 6-min walking distance-climb index (r = -0.77, p < 0.0001). The saturation deviation (mean of SpO(2) values <95 %) on the step test correlated with diffusion capacity of the lung (ρ = -0.49, p = 0.001). No correlations were found between the step test indices and other lung function tests, hemodynamic parameters or NT-proBNP levels. CONCLUSIONS: Patients with PAH/CTEPH have significant limitation in step climbing ability that correlates with functional class and 6-min walking distance. This is a significant impediment to their daily activities.

Prevalence and impact of coronary artery disease in patients with pulmonary arterial hypertension.

The occurrence and impact of coronary artery disease (CAD) among patients with pulmonary arterial hypertension (PAH) are unknown. We aimed to determine the prevalence, clinical correlates, and effect of CAD in patients with PAH. We reviewed the medical records of consecutive patients diagnosed with PAH at a university-based referral center for pulmonary vascular disease from January 1990 to May 2010. The patients systematically underwent right heart catheterization and coronary angiography as a part of their evaluation. The patients with PAH with CAD (defined as ≥50% stenosis in ≥1 major epicardial coronary artery) were compared to patients without CAD. Among the 162 patients with PAH, the prevalence of CAD was 28.4%. The presence of CAD was associated with older age (66.6 ± 11.5 vs 49.2 ± 14.0 years, p <0.001), systemic hypertension, and dyslipidemia. The patients with PAH and CAD had a lower mean pulmonary arterial pressure (44.6 ± 11.1 vs 49.2 ± 14.0 mm Hg; p = 0.02) than patients without CAD. During a median follow-up of 36 months, 73 patients died. The presence of CAD was a predictor of all-cause mortality on univariate analysis (hazard ratio 1.97, 95% confidence interval 1.21 to 3.20) but not on multivariate analysis, which identified older age (hazard ratio 1.03, 95% confidence interval 1.01 to 1.05) and right atrial pressure (hazard ratio 1.08, 95% confidence interval 1.03 to 1.14) as the only independent predictors. In conclusion, our study has demonstrated that CAD is common among patients with PAH. CAD prevalence increases with age, dyslipidemia, and hypertension, but we did not detect an independent prognostic effect of CAD on mortality.

Pandemic influenza (H1N1): impact on lung transplant recipients and candidates.

BACKGROUND: The year 2009 was notable for the outbreak of a novel strain of influenza A (H1N1). We report the outcomes of H1N1 infection in a large cohort of lung transplant (LTx) recipients and candidates. METHODS: This was a retrospective review of 22 suspected cases of H1N1 influenza screened using real-time polymerase chain reaction from nasal secretions. There were 15 confirmed cases (10 LTx recipients, 5 LTx candidates). RESULTS: All patients were treated with oseltamivir at the time of the first clinical assessment. In the LTx recipients group, 7 of the 10 confirmed cases were treated at home with oseltamivir alone. Three patients were admitted with complications (2 pneumonia, 1 acute rejection). Two patients required mechanical ventilation. Two patients had prolonged viral shedding. No deaths occurred among the LTx recipients. In the 5 LTx candidates with confirmed H1N1, 2 deaths occurred from pneumonia and acute respiratory distress syndrome. CONCLUSIONS: Influenza H1N1 had a significant complication rate amongst LTx recipients and a high mortality rate amongst LTx candidates.