Potential Therapeutic Role of Respiratory Muscle Training in Dyspnea Management of Cancer Survivors: A Narrative Review.

Dyspnea is a disabling symptom presented in approximately half of all cancer survivors. From a clinical perspective, despite the availability of pharmacotherapies, evidence-based effective treatments are limited for relieving dyspnea in cancer survivors. Preliminary evidence supports the potential of respiratory muscle training to reduce dyspnea in cancer survivors, although large randomized controlled studies are warranted. The aims of this article were to review the relevant scientific literature on the potential therapeutic role of respiratory muscle training in dyspnea management of cancer survivor, and to identify possible mechanisms, strengths and limitations of the evidence as well as important gaps for future research directions.

Cardiorespiratory Fitness and Incidence of Digestive System Cancers in Men.

PURPOSE: To assess the association between cardiorespiratory fitness (CRF) and incidence of digestive system cancers (DSCs) in men. METHODS: A prospective cohort of 4,540 men aged 55.2 ± 13.1 years who were free from malignancy at baseline was studied. Exposure was CRF quantified from treadmill exercise testing (individualized ramp protocol) in metabolic equivalents (METs). Incidence of DSCs was the primary outcome, utilizing medical records of any new diagnosed DSC. Cox proportional hazard analyses were conducted adjusting for established cancer risk factors. RESULTS: Mean CRF was 8.3 ± 3.5 METs. During 13 ± 7.6 years follow up, 250 (5.5%) DSC cases were diagnosed (colorectal = 163, gallbladder = 46, liver = 23, esophagus = 8, pancreas = 7 and other digestive organ cancers = 3). For each 1-MET increase in CRF there were 6% [Hazard Ratio = 0.94, 95% CI (0.91-0.98), p = 0.006], and 9% [Hazard Ratio = 0.91, 95% CI (0.85-0.97), p = 0.006] lower risks of DSC incidence in the total cohort and among men younger than 60 years old, respectively. Additionally, each 1-MET increase in CRF was associated with 9% lower risks of DSC incidence among never and current smokers. CRF was not associated with DSC incidence among men ≥ 60 years old and among former smokers. CONCLUSION: Higher CRF was associated with lower risk of DSC incidence in men, particularly in those younger than 60 years, and never and current smokers. These findings suggest that higher CRF has potential preventive benefits against the development of DSCs, although additional large studies are needed. CRF screening and achieving higher levels could serve as a complementary preventive strategy for public health.

Dyslipidemia paradox: Analysis from the veterans exercise testing study.

BACKGROUND: Dyslipidemia is a well-established cardiovascular disease (CVD) risk factor, although its association with mortality is less clear. This study aimed to assess the association between established dyslipidemia criteria [National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel (ATP) III] and all-cause mortality in men. METHODS: Prospective cohort study of 1,479 men aged 59.7±10.7 years was conducted between 1987 and 2012. At baseline, dyslipidemia markers of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed as an exposure. Cox proportional hazard models were analyzed adjusting for conventional health risk factors using all-cause mortality as an outcome. RESULTS: Mean and standard deviations of TC, LDL-C and HDL-C were 199.5±45.2, 149.4±47.4 and 44.3±12.2 mg/dL, respectively. During 8.9±4.5 years follow-up, 284 participants died. Compared to TC <200 mg/dL, levels of 200-239 mg/dL and ≥240 mg/dL were associated with 13% [hazard ratio (HR) = 0.87, 95% confidence intervals (CI) (0.66-1.1)] and 37% [HR = 0.63, 95% CI (0.44-0.92)] lower risks of mortality (p trend = 0.048), respectively. Compared to LDL-C <130 mg/dL, levels of 130-189 mg/dL and ≥190 mg/dL were associated with 26% [HR = 0.74, 95% CI (0.57-0.97)] and 32% [HR = 0.68, 95% CI (0.48-0.98)] lower risks of mortality (p trend = 0.044), respectively. Mean survival time was 0.9 to 1.9 years longer with higher TC and LDL-C categories (both p = 0.001). HDL-C was not associated with mortality. CONCLUSION: In reference to established dyslipidemia criteria, this study showed that higher TC and LDL-C were independently and paradoxically associated with lower risk of all-cause mortality and longer survival time in men. Along with previous reports, these novel findings support a rigorous reevaluation of evidence on dyslipidemia and health risks. Systematic review and meta-analysis are warranted for evidence-based recommendations on dyslipidemia for primary and secondary prevention of CVD.

Haemodynamic gain index and heart failure incidence- Prognostic and preventive value.

AIMS: Heart failure (HF) is a non-curable, life-threatening condition, characterized by impaired haemodynamic function and poor survival. This study aimed to assess the association between haemodynamic gain index (HGI) and HF incidence in men. METHODS AND RESULTS: Exposure was HGI, [(HRpeak*SBPpeak) - (HRrest*SBPrest)]/(HRrest*SBPrest) measured from treadmill exercise testing in 5539 men aged 59 ± 11.5 years who were free from HF at baseline. The outcome was the incidence of HF. Cox hazard models adjusted for established risk factors were analysed for the association between HGI and HF. During 14.3 ± 6 years of follow-up, 297 cases of HF occurred (average annual incidence rate 3.7 events per 1000 person-years) and average HGI was 1.6 ± 0.7 bpm/mmHg. In a continuous model, every one unit higher in HGI was associated with a 44% [hazard ratio 0.56, 95% confidence interval (0.45-0.69), P < 0.001] lower risk of HF incidence. In a categorical model, compared with those in quartile-4 (HGI > 2.0), those in quartile-3 (HGI 1.51-2.0), quartile-2 (HGI 1.05-1.5), and quartile-1 (HGI < 1.05) exhibited 70%, 220%, and 280% higher risks for developing HF, respectively (P trend < 0.001). CONCLUSION: HGI was found to be a strong predictor of HF incidence in men, supporting its prognostic value. Higher HGI was independently associated with lower risk of HF incidence, while low HGI could serve as a prognostic risk factor for HF. Integrating HGI in the screening and early detection paradigm and referring individuals with low HGI to exercise rehabilitation could potentially enhance public health and prevention strategies against HF.

The study assessed the risk association between haemodynamic gain index measured from treadmill exercise test and the incidence of heart failure in a prospective cohort of 5539 men. •Haemodynamic gain index was found to be a powerful predictor of heart failure incidence. •Higher haemodynamic gain index was independently associated with lower risk of developing heart failure, while low haemodynamic gain index could serve as a prognostic risk factor for heart failure.

Non-exercise estimated cardiorespiratory fitness and cancer incidence: The NIH-AARP diet and health study.

BACKGROUND: Non-exercise estimated cardiorespiratory fitness (NEE-CRF) has been shown to be associated with mortality, although its association with cancer incidence is unknown. The study aimed to assess the prospective association between NEE-CRF and cancer incidence in a large cohort of men and women. METHODS: The National Institutes of Health-American Association of Retired Persons diet and health study is a prospective cohort that included 402,548 participants aged 50-71 years who were free from cancer at baseline (1995-1996) (men (n = 238,835) and women (n = 163,713)) and were followed until December 31, 2015. The exposure variable was NEE-CRF expressed in metabolic equivalents. NEE-CRF was estimated using a validated equation of self-reported predictors on demographics and lifestyle behaviors derived from baseline questionnaires. Primary outcomes were total cancer incidence and incidence of prostate, breast, lung, and colorectal cancers. Cox proportional hazards models were analyzed for the association between NEE-CRF and cancer incidence outcomes adjusted for established cancer risk factors. RESULTS: During 13.7 ± 3.2 years of follow-up (mean ± SD), 64,344 men and 31,315 women developed a new cancer. For every 1-metabolic equivalent higher NEE-CRF, the hazard ratios and 95% confidence intervals (95%CIs) were 0.96 (95%CI: 0.94-0.97) and 0.88 (95%CI: 0.84-0.92) of total and colorectal cancer incidence among men, and 0.95 (95%CI: 0.93-0.97) and 0.94 (95%CI: 0.91-0.97) of total and breast cancer incidence among women, respectively (all p < 0.001). NEE-CRF was not associated with incidence of prostate and lung cancers in men or colorectal and lung cancers in women. CONCLUSION: These results suggest that higher CRF levels, as assessed by the applied non-exercise estimated method, may provide preventive benefits against the development of cancer, while low CRF could potentially serve as a modifiable cancer risk factor. Integrating NEE-CRF into screening paradigms and referring low-fit individuals to improve CRF could complement the public health prevention strategy against cancer.

Could sarcopenia-related mortality in end-stage renal disease be underpinned by the number of hospitalizations and cardiovascular diseases?

PURPOSE: To investigate the association between sarcopenia with the number of all-cause mortality, hospitalizations, and cardiovascular diseases in patients with end-stage renal disease (ESRD). METHODS: 247 patients with ESRD (women, n = 97) (66.6 ± 3.53 years) participated in this study. At baseline, all participants were measured with dual-energy X-ray absorptiometry and handgrip dynamometer and were prospectively followed up for 5 years. The European Working Group on Sarcopenia in Older People guidelines were utilized for Sarcopenia determination. Cox proportional hazard analysis adjusted for established risk factors was used to quantify the risk between Sarcopenia and all-cause mortality. RESULTS: Sixty-five participants (26%) were determined to have Sarcopenia at baseline and 38 (15%) have died during the follow-up. At baseline, Participants with Sarcopenia had lower body mass index and fat-free mass index. Moreover, through the 5-year follow-up, sarcopenic patients had higher number of cardiovascular disease (56.9% vs. 12.6%) and hospitalizations (93.8% vs. 49.5%) (all P < 0.0001). Sarcopenia was associated with significantly higher risk of mortality, [Hazard ratio = 3.3, (95% CI: 1.6-6.9), P = 0.001]. CONCLUSION: Sarcopenia may be a risk factor for hospitalizations, cardiovascular diseases, and all-cause mortality in patients with ESRD. These results provide support of the relevance in assessing sarcopenia in the clinical practice of chronic kidney disease and how muscle mass and strength may negatively impact the daily life of ESRD patients undergoing hemodialysis. Greater efforts at preventing muscle wasting and malfunctioning are needed through the worldwide healthcare system.

Non-exercise estimated cardiorespiratory fitness and mortality from all-causes, cardiovascular disease, and cancer in the NIH-AARP diet and health study.

AIMS: Impractical methods and relatively small cohort have limited the applications of non-exercise estimated cardiorespiratory fitness (NEE-CRF). This study aimed to assess the association between a pragmatic NEE-CRF method and mortality outcomes in a large prospective cohort. METHODS AND RESULTS: A total of 330 769 participants [men (n = 186 469) and women (n = 144 300)] aged 50-71 years from the NIH-AARP Diet and Health Study were assessed at baseline (1995-96) and prospectively followed until 31 December 2015 (14.9 ± 2.1 years). Non-exercise estimated cardiorespiratory fitness was estimated using pragmatic and previously validated equation, and Cox hazard analysis for mortality was conducted. Non-exercise estimated cardiorespiratory fitness was 9.9 ± 1.5 metabolic equivalents (METs) in men and 7.2 ± 1.6 METs in women. In total, 34 317 men and 20 295 women died during the follow-up. Higher NEE-CRF was associated with lower mortality risk from all-causes, cardiovascular disease, and cancer. Compared to the lowest quartile of NEE-CRF, the hazard ratios and 95% confidence interval for all-cause mortality in the second, third, and fourth quartiles were: 0.82 (0.79-0.84), 0.74 (0.72-0.77), and 0.70 (0.67-0.73) for men, and 0.84 (0.81-0.88), 0.78 (0.75-0.82), and 0.72 (0.68-0.77) for women (P trend <0.001 for all). For each 1-MET increase in NEE-CRF, risks for mortality due to cardiovascular disease and cancer were 0.85 (0.82-0.88) and 0.89 (0.87-0.91) in men, and 0.84 (0.81-0.88) and 0.89 (0.87-0.91) in women, respectively (P < 0.001 for all). CONCLUSION: Higher NEE-CRF is independently associated with lower mortality risk in a large prospective cohort of men and women. These results support the utility of the applied NEE-CRF method for risk stratification, prevention, and rehabilitation programs and application in large epidemiological studies.

Poor handgrip strength determined clinically is associated with falls in older women.

OBJECTIVES: To assess the association between poor handgrip strength (HGS) determined by clinical criterion and incidence of falls in older women. METHODS: The cohort included 195 women (68.1±6.2 years) who were assessed for HGS (Jamar Dynamometer) at baseline and were prospectively followed for 18 months. FNIH Sarcopenia threshold of HGS adjusted for body mass index (<0.56) was used for clinical determination of poor HGS. Association between poor HGS and incidence of falls was analyzed using Cox hazard models in the total cohort and in a stratified analysis by balance status. RESULTS: During the follow-up, 53 (27%) women experienced at least one fall. In a multivariable model, poor HGS was associated with approximately 3-fold increased risk for falls [Hazard Ratio (HR)=2.73, 95% Confidence Interval (CI)=1.28-5.82, p=0.009]. In a stratified analysis, women with impaired balance exhibited even greater risk for falls (HR=3.85, 95%CI=1.47-10.12, p=0.011), although no association was found in women with normal balance (p=0.459). CONCLUSIONS: Poor HGS based on clinical criterion is independently associated with higher risk of falls in older women, particularly in those with impaired balance. These results suggest potential prognostic value of FNIH Sarcopenia threshold for risk stratification and referring high-risk individuals to fall prevention programs.

Behavioral and Physiological Health-Related Risk Factors in College Students.

The purpose of this study was to assess the behavioral and physiological health-related risk factors in college students. A cross-sectional study was conducted in 1620 college students (21.3 ± 1.7 years, 897 males, and 723 females). Physical activity (PA), sitting time, body composition, cardiorespiratory fitness (CRF), muscular endurance (ME), and blood test were assessed. In the total sample, 15.2% were not meeting PA guidelines, 33% were sedentary, 13.3% were obese, 10.7% had low CRF, 36.8% had poor ME, 33.7% had dyslipidemia and 5.9% presented with prediabetes. Obesity and poor CRF were more prevalent in male students, whereas inactivity was more prevalent in female students. Individuals with poor CRF were more likely to be obese (odds ratio = 5.2, 95% CI = 3.5-7.8, P = .007 for male students, and 9.4, 95% CI = 1.5-57.8, P = .021 for female students). Sitting time positively correlated with fat percentage (fat%) and inversely with lean body mass (LBM) in male students, whereas ME inversely correlated with fat% and positively with LBM in female students. Although most students were active, significant prevalence of health-related risk factors were observed. Sedentary behavior and poor fitness were associated with a compromised body composition in both sexes. Improving fitness and reducing sedentary behavior in college students could be a public health strategy for health promotion and chronic diseases prevention.

Physical Activity, Cardiorespiratory Fitness, and Population-Attributable Risk.

OBJECTIVE: To determine population-attributable risk (PAR) and exposure impact number (EIN) for mortality associated with impaired cardiorespiratory fitness (CRF), physical inactivity, and other risk markers among veteran subjects. METHODS: The sample included 5890 male subjects (mean age 58±15) who underwent a maximal exercise test for clinical reasons between January 1, 1992, and December 31, 2014. All-cause mortality was the end point. Cox multivariable hazard models were performed to determine clinical, demographic, and exercise-test determinants of mortality. Population-attributable risks and EIN for the lowest quartile of CRF and for inactive behavior were analyzed, accounting for competing events. RESULTS: There were 2728 deaths during a mean ± standard deviation follow-up period of 9.9±5.8 years. Having low CRF (<5.0 metabolic equivalents [METs]) was associated with an approximate 3-fold higher risk of mortality and a PAR of 12.9%. Each higher MET achieved on the treadmill was associated with a 15% reduction in mortality (hazard ratio [HR]=0.85; 95% confidence interval [CI], 0.83 to 0.88; P<.001). Nearly half the sample was inactive, and these subjects had a 23% higher mortality risk and a PAR of 8.8%. The least fit quartile (<5.0 METs) had relative risks of ≈6.0 compared with the most-fit group (HR=5.99; 95% CI, 4.9 to 7.3). The least-active tertile had ≈2-fold higher risks of mortality vs the most active subjects (HR=1.9; 95% CI, 0.91 to 4.1). The lowest EIN was observed for low fitness (3.8; 95% CI, 3.4 to 4.3, P<.001), followed by diabetes, smoking, hypertension, and physical inactivity (all P<.001 except for diabetes, P=.008). CONCLUSION: Both higher CRF and physical activity provide protection against all-cause mortality in subjects referred for exercise testing for clinical reasons. Encouraging physical activity with the aim of increasing CRF would have a significant impact on reducing mortality.

Long-term outcomes of metallic endobronchial stents in lung transplant recipients are not affected by bacterial colonization.

OBJECTIVES: We evaluated associations of endobronchial stenting with airway bacterial colonization, the antimicrobial resistance profile, hospitalizations for pneumonia and survival in lung transplant recipients. METHODS: This is a retrospective single-centre study of 582 recipients of lung transplant during 2002-2018. We compared outcomes of 57 patients (9.7%) who received endobronchial stents (intervention group) to a control group of 57 patients without stents who were matched one to one for age, sex, year of transplantation, unilateral/bilateral transplantation and underlying disease. RESULTS: For the intervention compared to the control group, airway colonization was more common for Pseudomonas (86% vs 35%, P < 0.001), Acinetobacter (21% vs 7%, P = 0.05), Klebsiella (21% vs 5%, P = 0.02) and Staphylococcus species (11% vs 0%, P = 0.02). The respective proportions of patients with positive bronchoalveolar lavage cultures on the third post-transplantation day, the day of stent insertion and 6-month post-stent insertion were 47.4%, 50.9% and 65.4% for Pseudomonas sp.; 15.8%, 12.3% and 3.8% for Klebsiella sp.; and 8.8%, 5.3% and 5.8% for Acinetobacter sp. The mean number of hospitalizations for pneumonia per patient was higher, without statistical significance, in the intervention than the control group (1.5 ± 1.7 vs 0.9 ± 1.5, P = 0.1). Kaplan-Meier survival curves did not show a statistically significant difference between the intervention group and the entire group without endobronchial stents (n = 525) (P = 0.4). CONCLUSIONS: Lung transplant recipients with endobronchial stents were more likely to be colonized with pathologic bacteria and having pneumonia; however, stent placement was not associated with increased long-term mortality with appropriate stent maintenance.

Cardiorespiratory fitness and cancer in men with cardiovascular disease: Analysis from the Veterans Exercise Testing Study.

BACKGROUND: Cardiovascular disease and cancer share similar risk factors and are the leading causes of death worldwide. This study aimed to assess the association between cardiorespiratory fitness, cancer incidence and cancer mortality in men with cardiovascular disease. METHODS: Baseline cardiorespiratory fitness (treadmill exercise test) was assessed in 565 men aged 58.9 ± 17 with documented cardiovascular disease and free from any malignancy. Cox multivariable hazard models, population attributable fraction and exposure impact number were analyzed in model accounting for competing events for cancer outcomes. RESULTS: Mean cardiorespiratory fitness was 7.6 ± 3.4 metabolic equivalents. During a 12.0 ± 7.5 year follow-up, 147 participants developed any type of cancer, 70 died from cancer, and five died from causes other than cancer as competing events. Compared to low cardiorespiratory fitness (<5 metabolic equivalents), moderate (5-10 metabolic equivalents) and high cardiorespiratory fitness (>10 metabolic equivalents) were associated with 50% (0.50, 95% confidence interval (0.27-0.91)) and 68% (0.32 (0.11-0.88)) reduced risks for cancer mortality (p trend = 0.026), respectively. Survival time was longer among individuals with moderate (20.8 (19.7-22) years) and high (24.9 (23-26.7) years) compared to low cardiorespiratory fitness (17.2 (15.1-19.3) years), p < 0.001. Population attributable fraction and exposure impact number for cancer mortality were 13% (4.1-17.7) and 10.8 (5.1-56.4), p = 0.01, respectively. Cardiorespiratory fitness was not associated with cancer incidence. CONCLUSION: Higher cardiorespiratory fitness was independently associated with lower risk of cancer mortality and extended survival time in men with cardiovascular disease, although it was not associated with cancer incidence. Improving cardiorespiratory fitness through supervised exercise rehabilitation programs could potentially serve as a cost-effective public-health strategy for secondary prevention and survivorship in men with cardiovascular disease.

Retracted: Facemasks in the COVID-19 era: A health hypothesis.

Many countries across the globe utilized medical and non-medical facemasks as non-pharmaceutical intervention for reducing the transmission and infectivity of coronavirus disease-2019 (COVID-19). Although, scientific evidence supporting facemasks' efficacy is lacking, adverse physiological, psychological and health effects are established. Is has been hypothesized that facemasks have compromised safety and efficacy profile and should be avoided from use. The current article comprehensively summarizes scientific evidences with respect to wearing facemasks in the COVID-19 era, providing prosper information for public health and decisions making.

Clinical Improvement and Effectiveness of Exercise-Based Pulmonary Rehabilitation in Patients With Idiopathic Pulmonary Fibrosis: A BRIEF ANALYTICAL REVIEW.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease associated with high mortality rates and poor clinical condition. Exercise-based pulmonary rehabilitation (EBPR) has been demonstrated to be effective in improving 6-min walk distance (6MWD), although the clinical improvement and effectiveness are less characterized. The current review examined the existing evidence of EBPR among patients with IPF and aimed to analyze the effect of EBPR on clinical improvement and effectiveness. METHODS: A systematic databases search (MEDLINE/PubMed, EMBASE, and the Cochrane Library) was conducted for available publications as of January 2020. Randomized controlled trials (RCTs) and meta-analyses of RCTs examining the effect of EBPR in patients with IPF were reviewed. Mean difference for RCTs and weighted mean difference for meta-analyses between the EBPR arm and the usual-care arm in 6MWD were compared with the established minimal clinically important difference (MCID) of 30 m. Clinical improvement following EBPR was determined when mean difference and weighted mean difference were equal or exceeding the MCID. Effectiveness of EBPR was assessed using the number needed to treat (NNT) analysis. RESULTS: Five independent RCTs (including 21-61 patients/study) and five meta-analyses (including two to five studies with 62-169 patients/meta-analysis) were included. The mean difference of 6MWD ranged from 16-81 m in RCTs. Three of five RCTs demonstrated an average improvement that meets or exceeds the MCID. Two RCTs showed favorable improvement in 6MWD but did not reach the MCID. The weighted mean difference of 6MWD ranged from 27-49 m in the meta-analyses. Four of five meta-analyses showed an average improvement that meets or exceeds the MCID. One early meta-analysis of only two RCTs showed significant improvement, although did not reach the MCID. The NNT in three RCTs and four meta-analyses that met clinical improvement in 6MWD was one. CONCLUSIONS: This review provides novel evidence with respect to clinical improvement and high effectiveness of EBPR among patients with IPF. The results suggest that, on average, the majority of patients would be expected to clinically improve by completing the EBPR program. The findings further support the prescription of EBPR as clinically effective therapy and implementation as standard of care for patients with IPF. Future studies examining clinical improvement and effectiveness utilizing additional outcomes with the MCID are warranted.

Hemodynamic gain index in women: A validation study.

BACKGROUND: A previous study showed a strong and independent association between hemodynamic gain index (HGI) and all-cause mortality in a large cohort of men. The current study aimed to validate the association between HGI and all-cause mortality in a pilot cohort of women. METHODS: The cohort included 606 women aged 54.1 ± 12 years who were prospectively followed for 8.0 ± 5.7 years. HGI was calculated according to a previously developed equation using heart rate (HR) and systolic blood pressure (SBP) responses from treadmill exercise testing [(HRpeak*SBPpeak)-(HRrest*SBPrest)]/(HRrest*SBPrest). Bivariable and multivariable Cox hazard models were analyzed for HGI and all-cause mortality. RESULTS: During the follow-up, 48 participants (7.9%) died, and mean HGI was 1.86 ± 0.82 bpm/mmHg. In continuous bivariable and multivariable models, each one unit higher in HGI was associated with 64% and 45% reduced risks of mortality, respectively. The corresponding hazard ratios and 95% confidence intervals were: 0.36, (0.22-0.57), and 0.55 (0.33-0.91) (both p < 0.001). In a bivariable categorical model, compared to participants below the 25th percentile (HGI <1.27), participants who were between the 25th and 50th (HGI 1.27 to 1.77), 50th to 75th (HGI 1.78 to 2.39) and >75th percentile (HGI ≥2.4) exhibited 57%, 90% and 79% reductions in mortality risk (p trend <0.001), respectively. CONCLUSIONS: This validation study in women confirms that a higher HGI is associated with lower risk of all-cause mortality, supporting its prognostic value for risk stratification in clinical and research settings.

The Etiology and Prognosis of Delayed Postoperative Leukocytosis in Lung Transplant Recipients.

BACKGROUND: Leukocytosis (white blood cell count >12 000/µL) in the delayed postoperative period (4-7 days) after lung transplantation is due to diverse etiologies. We aimed to describe the etiologies of delayed postoperative leukocytosis in lung transplant recipients and to evaluate the association of leukocytosis causes with short-term survival. METHODS: A retrospective chart review of 274 lung transplantations performed in our institution during 2006 to 2013. RESULTS: Delayed postoperative leukocytosis was seen in 159 (58.0%) of lung transplant recipients. In 57 (35.8%) of them, the etiology of the leukocytosis was not identified. The etiologies of leukocytosis that were identified were infection (n = 39), second surgery, acute rejection (n = 12), primary graft dysfunction (n = 3), multiple etiologies (n = 17), and other causes (n = 10). On multivariate analysis, delayed postoperative leukocytosis was one of the variables that most significantly associated with decreased survival in the entire sample (hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.01-2.29, P = .040). On additional analysis for mortality assessing each leukocytosis subgroup, the data were acute graft rejection (HR = 8.21, 95% CI: 4.09-16.49, P < .001), second surgery (HR = 2.05, 95% CI: 1.08-3.90, P = .020), primary graft dysfunction (HR = 2.72, 95% CI: 0.65-11.33, P = .169), other causes (HR = 1.30, 95% CI: 0.47-3.62, P = .620), and unknown etiology (HR = 0.94, 95% CI: 0.54-1.62, P = .800). CONCLUSIONS: Delayed post-lung transplant leukocytosis is a poor prognostic sign, especially when attributed to acute graft rejection, infection, and multiple etiologies. In the absence of an identifiable etiology, it can be attributed to postoperative reactive stress, is not associated with increased mortality, and likely does not warrant further diagnostic investigation.

Routine comprehensive Aspergillus screening of bronchoalveolar lavage samples in lung transplant recipients.

BACKGROUND: Invasive aspergillosis is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). Early diagnosis may improve outcome, yet is challenging. We assessed the diagnostic yield of a routine, comprehensive, prospectively employed Aspergillus screening strategy in LTRs. METHODS: During a 6-month period, all bronchoalveolar lavage (BAL) samples (including post-transplant surveillance) obtained from LTRs at our center were routinely tested for Aspergillus PCR, galactomannan (GM), and fungal culture. Invasive aspergillosis (IA) was defined using EORTC/MSG and ISHLT criteria for proven and probable aspergillosis. RESULTS: Ninety-five consecutive BAL samples were tested. PCR, GM, and fungal culture were positive in 28.4%, 30.6%, and 7.4%, respectively. Five cases of IA (two proven, three probable) were identified. Fungal culture failed to detect 40% of IA cases, which were detected by a positive PCR and/or GM. However, the majority of positive PCR samples represented colonization (59.3%). Sensitivity of PCR, GM, and culture for IA was 80%, 60%, and 60%, respectively, and specificity was 74%, 71%, and 96%. CONCLUSIONS: In LTRs, a routine prospectively employed screening strategy in which all BAL samples were screened for Aspergillus PCR and GM, detected aspergillosis cases that were otherwise missed by a false-negative fungal culture, but resulted in more cases of colonization being detected. Clinical judgment is thus warranted to avoid unnecessary treatment of colonization.

The preventive role of cardiorespiratory fitness in current male smokers who meet the American Cancer Society criteria for lung cancer screening: a prospective pilot study.

PURPOSE: Survival benefits could be potentially improved by adding cardiorespiratory fitness (CRF) to lung cancer screening. The current pilot study aimed to assess the association between CRF and adverse outcomes in current male smokers who are meeting the American Cancer Society (ACS) criteria for lung cancer screening. METHODS: A total of 260 men with a baseline CRF assessment (treadmill exercise test) who are met the ACS lung cancer screening criteria ("current smokers aged 55-74 years with ≥ 30 pack/years smoking history") were prospectively studied. Cox proportional hazard models were analyzed for all-cause and cancer mortality, total and lung cancer incidence. RESULTS: Mean age was 63.3 ± 5.4 years, smoking history 50.4 ± 26.7 pack/years, and CRF was 7.8 ± 3.2 metabolic equivalents (METs). During a mean of 10.2 ± 6.1 years follow-up, 80 participants developed any type of cancer, 19 were diagnosed with lung cancer and 66 died (cancer, n = 39, other causes, n = 27). In multivariable models, only CRF was associated with all-cause and cancer mortality. Each 1-MET higher CRF was associated with a 10% reduced risk for all-cause mortality [0.9, 95% CI (0.83 to 0.98), p = 0.017] and cancer mortality [0.9, 95% CI (0.8 to 0.99), p = 0.048]. CRF was not associated with total cancer incidence (p = 0.59) or lung cancer incidence (p = 0.96). CONCLUSION: Higher CRF is independently associated with lower risk of all-cause and cancer mortality in current male smokers who meet the ACS criteria for lung cancer screening. Screening for CRF and achieving higher CRF levels could potentially reduce mortality and serve as complementary preventive strategy in heavy smokers.

Reference Standards for Ventilatory Threshold Measured With Cardiopulmonary Exercise Testing: The Fitness Registry and the Importance of Exercise: A National Database.

BACKGROUND: Established reference standards for the ventilatory threshold (Vt) are lacking. The aim of this study was to develop reference standards for the Vt derived from cardiopulmonary exercise testing (CPX) using treadmill and cycle ergometry. METHODS: Seven laboratories experienced in CPX administration with established quality control procedures contributed to the Fitness Registry and the Importance of Exercise: A National Database (FRIEND) from April 2014 through February 2019. Vt data from 27 states in the United States and the Ontario Province in Canada, comprising 9,350 tests (treadmill: n = 1,195; cycle ergometer: n = 8,155) in men (n = 7,540) and women (n = 1,810) 20 to 79 years of age who were free from smoking and known cardiovascular, pulmonary, metabolic, and/or neoplastic disease were used to develop the reference standards. Comparisons of Vt values were made between exercise testing modes, sex, and age groups. RESULTS: Vt values on the treadmill were higher than cycle ergometry; men had higher Vt values than women on both test modalities, and the highest Vt values achieved were in the 20- to 29-year-old age group compared with all other age groups (all P < .001). The rates of decline in Vt values from age groups 20 to 29 through 70 to 79 years of age were 23% and 35% in men and 47% and 30% in women for treadmill and cycle ergometry tests, respectively. CONCLUSIONS: In addition to previous reference standards from FRIEND for cardiorespiratory fitness, the Vt reference standards reported herein provide valuable information on functional metric. These data have important implications for CPX interpretation and aerobic exercise prescription in the clinical and fitness settings.