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.

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.

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.

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.

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.

Soluble tumor necrosis factor receptor: enbrel (etanercept) for subacute pulmonary dysfunction following allogeneic stem cell transplantation.

Subacute lung disease, manifested as either obstructive (OLD) or restrictive (RLD) lung dysfunction, is a common complication following allogeneic stem cell transplantation. In each case, therapeutic options are limited, morbidity remains high, and long-term survival is poor. Between 2001 and 2008, 34 patients with noninfectious, obstructive (25) or RLD restrictive lung dysfunction (nine) received etanercept (Enbrel®, Amgen Inc.) 0.4 mg/kg/dose, subcutaneously, twice weekly, for 4 (group A) or 12 weeks (group B). Corticosteroids (if present at study entry) were kept constant for the initial 4 weeks of therapy and then tapered as tolerated. Thirty-one of 34 (91%) subjects were evaluable for response, and 10 (32%) met primary response criteria. There was no difference in response based on the duration of treatment (29% group A versus 35% group B; P = .99), the presence of RLD or OLD (33% versus 32%; P = .73), or the severity of pulmonary disease at study onset. Estimated 5-year overall survival rates following therapy were 61% (95% confidence interval, 46%-80%) for all subjects and 90% (95% confidence level, 73%-100%) for the 10 who met the primary response criteria. Five-year survival estimates for subjects treated with RLD was 44%, compared with 67% for those treated for OLD (P = .19). Etanercept was well tolerated, with no bacteremia or viremia observed. Pathogens were noted on posttherapy bronchoalveolar lavage in two cases. These data support the development of expanded clinical trials to study etanercept as a therapeutic agent for subacute lung injury after allogeneic stem cell transplantation.

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and health deterioration. It is associated with significant morbidity, mortality and health system burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for COPD patients in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and medical service utilisation. SEARCH METHODS: The Cochrane Airways Group Specialised Register of Trials was searched (November 2011). Study references were hand-searched for additional studies we contacted study authors to identify other unpublished studies. SELECTION CRITERIA: We included only randomised controlled trials of COPD patients. We included interventions involving an outreach nurse visiting patients in their homes, providing support, education, monitoring health and liaising with physicians. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: We pooled mortality data from eight studies and found a non-significant reduction in mortality at 12 months (OR 0.72, 95% CI 0.45 to, 1.15).We pooled four studies that assessed disease-specific heath-related quality of life (HRQL) and found a statistically significant improvement in HRQL (mean difference -2.61, 95% CI -4.82 to -0.40).Hospitalisations were reported in five studies. Although there was no statistically significant difference in the number of hospitalisations (OR 1.01, 95% CI 0.71 to 1.44), there was significant heterogeneity. Although this heterogeneity appeared to be caused by one outlying study with a statistically significant decrease in hospitalisations in patients receiving home care, whereas the other studies showed a non-significant increase in hospitalisations, we could not draw firm conclusions about why this heterogeneity exists. Data on GP visits and emergency department presentations were available, however no consistent effect in these was observed with the intervention. The intervention also incurred higher health care costs than standard care as reported in a single study.Very few studies provided data on lung function or exercise performance, so there was insufficient evidence to assess impact on these outcomes. AUTHORS' CONCLUSIONS: Outreach nursing programmes for COPD improved disease-specific HRQL. However the effect on hospitalisations was heterogeneous, reducing admissions in one study, but increasing them in others, therefore we could not draw firm conclusions for this outcome.

Forced vital capacity, airway obstruction and survival in a general population sample from the USA.

BACKGROUND: Many studies show a link between forced expiratory volume in 1 s (FEV(1)) and survival in the general population and this has been interpreted as a link between airway obstruction and survival. However, the observation that vital capacity is also associated with survival weakens this interpretation. METHODS: Data on spirometry and survival were taken from the Atherosclerosis Risk in Communities (ARIC) limited access dataset. Survival among 7489 participants with usable spirometry and complete data was regressed against measures of ventilatory function after controlling for many other factors likely to be associated with survival. RESULTS: Survival was strongly associated with forced vital capacity (FVC) after adjustment for FEV(1), but not the other way round. The fully adjusted hazard ratio (HR) associated with high FVC was 0.90 in men (95% CI 0.80 to 1.00; p=0.049) and 0.82 in women (95% CI 0.70 to 0.95; p=0.01). This compares with 0.98 for FEV(1) in men (95% CI 0.90 to 1.07; p.0.72) and 1.01 in women (95% CI 0.89 to 1.15; p=0.84). There was no association between survival and airway obstruction as measured by the FEV(1)/FVC ratio. CONCLUSIONS: FVC but not airway obstruction predicts survival in asymptomatic adults without chronic respiratory diagnoses or persistent respiratory symptoms. The association is not explained by age, anthropometry, smoking, income occupation or blood pressure. As FVC later in life, cardiovascular risk, type II diabetes mellitus and low-grade systemic inflammation are all associated with poor fetal growth, these other conditions may be partly responsible for the poor survival in those with low FVC.

Home care by outreach nursing for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction, worsening exercise performance and health deterioration. It is associated with significant morbidity, mortality and health system burden. OBJECTIVES: To evaluate the effectiveness of outreach respiratory health care worker programmes for COPD patients in terms of improving lung function, exercise tolerance and health related quality of life (HRQL) of patient and carer, and reducing mortality and medical service utilisation. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register of Trials was searched (November 2009). Study references were hand-searched for additional studies we contacted study authors to identify other unpublished studies. SELECTION CRITERIA: We included only randomised controlled trials of COPD patients. We included interventions involving an outreach nurse visiting patients in their homes, providing support, education, monitoring health and liaising with physicians. Studies in which the therapeutic intervention under test was physical training were not included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: We included five new studies in this update, resulting in a total of nine included studies.We pooled mortality data from eight studies and found a non-significant reduction in mortality at 12 months (OR 0.72, 95% CI 0.45 to, 1.15).We pooled four studies that assessed disease-specific heath-related quality of life (HRQL) and found a statistically significant improvement in HRQL (mean difference -2.61, 95% CI -4.82 to -0.40).Hospitalisations were reported in five studies. Although there was no statistically significant difference in the number of hospitalisations (OR 1.01, 95% CI 0.71 to 1.44), there was significant heterogeneity. Although this heterogeneity appeared to be caused by one outlying study with a statistically significant decrease in hospitalisations in patients receiving home care, whereas the other studies showed a non-significant increase in hospitalisations, we could not draw firm conclusions about why this heterogeneity exists. Data on GP visits and emergency department presentations were available, however no consistent effect in these was observed with the intervention. The intervention also incurred higher health care costs than standard care as reported in a single study.Very few studies provided data on lung function or exercise performance, so there was insufficient evidence to assess impact on these outcomes. AUTHORS' CONCLUSIONS: Outreach nursing programmes for COPD improved disease-specific HRQL. However the effect on hospitalisations was heterogeneous, reducing admissions in one study, but increasing them in others, therefore we could not draw firm conclusions for this outcome.

[Main causes of death among Polish population in 2030]. / Najwazniejsze przyczyny zgonów Polaków w 2030 roku.

The purpose of the study was the identification of main causes of death in Poland in 2030 and the assessment of mortality associated with them. It was assumed that the population age structure in 2030 shall develop in accordance with the prognosis of the Central Statistical Office. Mortality level was estimated using the projections for the regions (groups of countries), defined on the basis of some geographical and economic criteria, published by WHO as the result of the Global Burden of Disease Study. It was found that in 2030 mortality in Poland will increase by 17%-25% in comparison to 2008 which will be the result of changes in the age structure of the population. At the same time, the risk of death, expressed by age specific mortality rates, will decrease. Similar effects are expected for particular main causes of death. Ischaemic heart disease and cerebrovascular diseases will continue to account for the most frequent reasons of death. In comparison to 2008 a significant increase of mortality due to diabetes mellitus and prostate cancer will be observed. According to some projections, it will also refer to the chronic obstructive pulmonary disease as well as malignant neoplasms of colon, rectum and stomach. Mortality due to suicides and road traffic accidents will decrease.

Morbidity and mortality associated with the restrictive spirometric pattern: a longitudinal study.

BACKGROUND: Recent studies have suggested that a restrictive pattern assessed with a single spirometric test is associated with increased morbidity and mortality. This study was undertaken to determine demographic, clinical and mortality profiles of subjects with either a recurrent or an inconsistent restrictive spirometric pattern assessed prospectively. METHODS: Data from 2048 adult participants in the population-based TESAOD study were analysed. Normal (forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) ratio >or=70% and FVC >or=80% predicted), restrictive (FEV(1)/FVC >or=70% and FVC <80% predicted) and obstructive (FEV(1)/FVC <70%) patterns were assessed at the enrollment survey in 1972 and in 11 subsequent follow-up surveys up to 1996. Demographic and clinical characteristics were measured at enrollment and vital status and cause of death were assessed at January 2005. RESULTS: Overall, 12% of participants had a restrictive spirometric pattern at enrollment. They were less likely to be male, to smoke and to have asthma, and had lower IgE levels than subjects in the obstructive group. Among subjects with a restrictive pattern at enrollment, 38% developed an obstructive pattern during follow-up. The remaining 62% had either a recurrent (restrictive pattern >or=50% of follow-up surveys) or inconsistent (restrictive pattern <50% of follow-up surveys) longitudinal restrictive pattern. The recurrent and inconsistent restrictive groups had increased mortality risk for all-cause (adjusted HR 1.7 (95% CI 1.3 to 2.3) and 1.9 (95% CI 1.4 to 2.6), respectively), heart disease (2.0 (95% CI 1.3 to 3.1) and 2.7 (95% CI 1.7 to 4.3)), stroke (2.4 (95% CI 0.9 to 6.3) and 3.5 (95% CI 1.2 to 9.8)) and diabetes (8.0 (95% CI 2.9 to 21.8) and 6.0 (95% CI 1.9 to 19.2)). CONCLUSIONS: The restrictive spirometric pattern identifies a pulmonary condition that is distinguishable from obstructive lung disease and is associated with an increased risk of life-threatening comorbidities.

Obesity and mortality in persons with obstructive lung disease using data from the NHANES III.

OBJECTIVES: The objective of this study was to determine the relationship between obesity and all-cause mortality among participants with obstructive lung disease in the National Health and Nutrition Examination Survey (NHANES III). METHODS: Public data from a retrospective cohort of the 33,994 participants in NHANES III was analyzed to determine the relationship between obesity and all-cause mortality among participants with obstructive lung disease. Results were analyzed using proportional hazard models and controlled for age, sex, race, smoking status, current oral corticosteroid use, and severity of airway obstruction. Secondary analysis considered time until death from respiratory disease or time until death from chronic lower respiratory disease (excluding asthma). RESULTS: The subset used in the analysis consisted of 2439 persons with 844 documented deaths. Extreme obesity (body mass index [BMI] >40) was significantly associated with increased respiratory disease mortality (hazard ratio [HR] 5.78; 95% confidence interval {CI} [1.09 to 30.61]) and chronic lower respiratory disease mortality (HR 13.69; 95% CI [1.45 to 129.29]). In addition, underweight status (BMI <18.5) was significantly associated with increased all-cause mortality (HR 2.42; 95% CI [1.31 to 4.46]), respiratory disease mortality (HR 7.10; 95% CI [1.94 to 26.00]) and chronic lower respiratory disease mortality (HR 14.80; 95% CI [2.24 to 97.99]). CONCLUSION: Underweight adults had increased risk of death from all causes and respiratory conditions, compared to class I obese adults. Extreme obesity was associated with increased risk of death from respiratory conditions, but not all-cause mortality. Additional research is needed to explain the complex relationship between BMI and specific causes of mortality in the context of pulmonary disease.

[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.

Prospective risk-adjusted morbidity and mortality outcome analysis after therapeutic bronchoscopic procedures: results of a multi-institutional outcomes database.

INTRODUCTION: Interest in databases is growing to allow for outcomes research, assess health-care quality, and determine best practices and resource allocation, and they are increasingly considered as a tool to potentially tie reimbursement to outcome parameters. Little is known about resource use and risk-adjusted morbidity and mortality after therapeutic bronchoscopic interventions. METHODS: Data were extracted and reviewed from an ongoing prospective, multi-institutional outcomes database for therapeutic bronchoscopic interventions. All consecutive patients are entered into this database, and information on demographics, indications, procedures and anesthesia, comorbidities and general health status, urgency of intervention, morbidity and mortality to 30 days, increase in levels of care, and procedural resources is documented. RESULTS: From December 2005 to May 2007, 554 therapeutic procedures were performed in four hospitals. Most procedures were done under general anesthesia (n = 362) and rigid bronchoscopy (n = 483), and the most common intervention was airway stent placement (n = 258). Forty-two percent of procedures were done urgently or emergently. Complications were common (19.8%), and 30-day mortality was 7.8%, correlating with underlying health status and urgency of intervention. DISCUSSION: Prospective and ongoing data analysis for bronchoscopic procedures is feasible and valuable. Risk-adjusted and disease-specific outcomes can be documented and potentially used for quality assessment, benchmarking, and quality improvement initiatives. Appropriate use of resources and effect of interventions can be documented. Extending the number of participating centers as well as inclusion of quality of life tools and technical success are the next steps.

Restrictive pulmonary dysfunction at spirometry and mortality in the elderly.

OBJECTIVES: To evaluate the association between pulmonary restriction and mortality in the elderly, taking into account potential confounders not considered in the past (disability, cognitive dysfunction, diabetes, and visceral obesity). DESIGN: Longitudinal study. SETTING: Community-based. PARTICIPANTS: Twelve hundred sixty-five patients (51.9% men) aged 65-97 years old from the Salute Respiratoria nell'Anziano (SaRA) Italian multicentric study. MEASUREMENTS: Participants were divided in 4 groups: normal spirometry (NS): FEV1/FVC > or = 70%, FVC > or = 80% of predicted; restrictive ventilatory pattern (RVP): FEV1/FVC > or = 70%, FVC<80%; obstructive ventilatory pattern (OVP): FEV1/FVC < 70%, FVC > or = 80%, and mixed ventilatory pattern (MVP): FEV1/FVC < 70%, FVC < 80%. We calculated the association between restriction and mortality corrected for potential confounders using a multivariable Cox regression model. RESULTS: We found a prevalence of RVP, OVP and MVP of 10.9%, 25.4%, and 17.3%, respectively. Compared to people with normal spirometric pattern, disability (19.6% vs. 10.1%), poor physical performance (35.4% vs. 22.3%), cognitive impairment (21.0% vs. 11.5%), increased waist circumference (62.1% and 26.8%), and kyphoscoliosis (56.8 and 13.5%) were more prevalent in the RVP group. After correction for potential confounders, RVP was associated with increased mortality (HR: 1.89; 95% CI: 1.15-3.11), as well as OVP (HR: 2.33; 95% CI: 1.58-3.11) and MVP (HR: 2.60; 95% CI: 1.74-3.93). Other factors associated with mortality were disability (HR: 1.92; 95% CI: 1.35-2.72), poor physical performance (HR: 1.37; 95% CI: 1.01-1.85), cognitive impairment (HR: 1.55; 95% CI: 1.06-2.27), depression (HR: 1.57; 95% CI: 1.16-2.13) and diagnosis of stroke (HR: 1.90; 95% CI: 1.18-3.05). CONCLUSIONS: RVP is associated with higher mortality in the elderly and, thus, deserves the same attention paid to an obstructive pattern. However, mechanisms mediating this association need to be clarified.

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.

Secondhand smoke exposure, pulmonary function, and cardiovascular mortality.

PURPOSE: Cardiovascular disease and obstructive lung disease are leading global causes of death. Despite this, the impact of secondhand smoke (SHS) exposure on pulmonary function and cardiovascular disease remains uncertain. Our goal was to elucidate the association between baseline SHS exposure and the risk of lung function decline and cardiovascular mortality over a period of nearly a decade. METHODS: We used data from a longitudinal cohort study of 1,057 older adults to study the association between baseline SHS exposure and the risk of lung function decline and cardiovascular mortality. The effect of SHS exposure on cardiovascular mortality may be mediated by its influence on FEV1 and biological processes captured by measurement of FEV1. Alternatively, the effect of SHS may be mediated by baseline cardiovascular disease status, which reflects the combined effects of traditional cardiovascular risk factors. To correctly estimate the effect of SHS and FEV1 on cardiovascular mortality, we used marginal structural models (MSMs) that took into account the mediating effects of FEV1 and baseline cardiovascular disease in the causal pathway. RESULTS: In longitudinal multivariate analyses, lifetime cumulative home and work SHS exposure were associated with a greater decline of FEV1 (-15 mL/s; 95% CI, -29 to -1.3 mL/s and -41 mL/s; 95% CI, -55 to -28 mL/s per 10-year cumulative exposure, respectively). Lifetime home SHS exposure was associated with a greater risk of cardiovascular mortality in both conventional multivariate analysis (HR, 1.10 per 10 years of exposure; 95% CI, 0.99 to 1.24) and the MSM for FEV1 (HR, 1.06; 95% CI, 0.95 to 1.19) and baseline cardiovascular disease (HR for subjects with no baseline cardiovascular disease, 1.39; 95% CI, 1.17 to 1.66). CONCLUSIONS: Lifetime SHS exposure appears to result in a greater decline in lung function and risk of cardiovascular mortality, taking into account confounders and the mediating effect of FEV1 and baseline cardiovascular disease.

Avoidable mortality in Victoria between 1979 and 2001.

OBJECTIVE: To describe trends in avoidable mortality (AM) in Victoria by sex, degree of socio-economic disadvantage and remoteness. METHODS: The analysis is based on mortality and population data for 1979-2001 supplied by the Australian Bureau of Statistics (ABS) for Victoria. Total and disease-specific AM rates were age standardised using the direct method. For the period between 1997 and 2001, comparisons of total AM rates by sex were made between metropolitan and rural local government areas (LGAs), and between LGAs grouped into quintiles based on socio-economic disadvantage and categories of remoteness. RESULTS: Total AM rates declined significantly (p < 0.05) in both males and females between 1979 and 2001, but were significantly higher in males compared with females. Total AM rates were significantly higher in rural compared with metropolitan LGAs, from 1997 to 2001 in males and in 1998 in females. Total AM rates in the least disadvantaged quintile were significantly lower than those in the most disadvantaged quintile over the entire five-year period in males and in three years in females. Total AM rates were highest in remote LGAs and lowest in highly accessible LGAs. There were significant declines in ischaemic heart disease, stroke and road traffic accident AM rates among males. In females, IHD, stroke, breast and colon cancer AM rates declined significantly. CONCLUSIONS AND IMPLICATIONS: Despite large declines in AM in Victoria, there are significant differences in rates between the sexes and in the population based on socio-economic status or remoteness. These results provide opportunities for policy makers to prioritise public health and health services interventions, targeting population groups and specific disease conditions to reduce health inequalities.