Mounting evidence has firmly established that low levels of cardiorespiratory fitness (CRF) are associated with a high risk of cardiovascular disease, all-cause mortality, and mortality rates attributable to various cancers. A growing body of epidemiological and clinical evidence demonstrates not only that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, high cholesterol, and type 2 diabetes mellitus, but that the addition of CRF to traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The purpose of this statement is to review current knowledge related to the association between CRF and health outcomes, increase awareness of the added value of CRF to improve risk prediction, and suggest future directions in research. Although the statement is not intended to be a comprehensive review, critical references that address important advances in the field are highlighted. The underlying premise of this statement is that the addition of CRF for risk classification presents health professionals with unique opportunities to improve patient management and to encourage lifestyle-based strategies designed to reduce cardiovascular risk. These opportunities must be realized to optimize the prevention and treatment of cardiovascular disease and hence meet the American Heart Association's 2020 goals.

Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association.

2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

2018 AHA/ACC guideline for the management of adults with congenital heart disease [Clinical Practice Guideline]

This systematic review examined the measurement properties of the 6-min walk test (6MWT), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with chronic respiratory disease. Studies that report the evaluation or use of the 6MWT, ISWT or ESWT were included. We searched electronic databases for studies published between January 2000 and September 2013. The 6-min walking distance (6MWD) is a reliable measure (intra-class correlation coefficients ranged from 0.82 to 0.99 in seven studies). There is a learning effect, with greater distance walked on the second test (pooled mean improvement of 26 m in 13 studies). Reliability was similar for ISWT and ESWT, with a learning effect also evident for ISWT (pooled mean improvement of 20 m in six studies). The 6MWD correlates more strongly with peak work capacity (r50.59-0.93) and physical activity (r50.40-0.85) than with respiratory function (r50.10-0.59). Methodological factors affecting 6MWD include track length, encouragement, supplemental oxygen and walking aids. Supplemental oxygen also affects ISWT and ESWT performance. Responsiveness was moderate to high for all tests, with greater responsiveness to interventions that included exercise training. The findings of this review demonstrate that the 6MWT, ISWT and ESWT are robust tests of functional exercise capacity in adults with chronic respiratory disease.

https://erj.ersjournals.com/content/erj/44/6/1447.full.pdf

An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease

This text is a Stata-specific treatment of generalized linear mixed models, also known as multilevel or hierarchical models. These models are "mixed" in the sense that they allow fixed and random effects and are "generalized" in the sense that they are appropriate not only for continuous Gaussian responses but also for binary, count, and other types of limited dependent variables.

Multilevel and Longitudinal Modeling Using Stata, 3rd Edition

Both Peak Oxygen Uptake (peak VO2), from cardiopulmonary exercise testing (CPET) and the distance walked during a Six-Minute Walk Test (6 MWD) are used for following the natural history of various diseases, timing of procedures such as transplantation and for assessing the response to therapeutic interventions. However, their relationship has not been clearly defined. We determined the ability of 6 MWD to predict peak VO2 using data points from 1,083 patients with diverse cardiopulmonary disorders. The patient data came from a study we performed and 10 separate studies where we were able to electronically convert published scattergrams to bivariate points. Using Linear Mixed Model analysis (LMM), we determined what effect factors such as disease entity and different inter-site testing protocols contributed to the magnitude of the standard error of estimate (SEE). The LMM analysis found that only 0.16 ml/kg/min or about 4% of the SEE was due to all of the inter-site testing differences. The major source of error is the inherent variability related to the two tests. Therefore, we were able to create a generalized equation that can be used to predict peak VO2 among patients with different diseases, who have undergone various exercise protocols, with minimal loss of accuracy. Although 6 MWD and peak VO2 are significantly correlated, the SEE is unacceptably large for clinical usefulness in an individual patient. For the data as a whole it is 3.82 ml/kg/min or 26.7% of mean peak VO2. Conversely, the SEE for predicting the mean peak VO2 from mean 6 MWD for the 11 study groups is only 1.1 ml/kg/min. A generalized equation can be used to predict peak VO2 from 6 MWD. Unfortunately, like other prediction equations, it is of limited usefulness for individual patients. However, the generalized equation can be used to accurately estimate mean peak VO2 from mean 6 MWD, among groups of patients with diverse diseases without the need for cardiopulmonary exercise testing. The equation is:

/pdf/the-six-minute-walk-test-accurately-estimates-mean-peak-2fqouq6mj4.pdf

The six minute walk test accurately estimates mean peak oxygen uptake

Traumatic brain injury (TBI) is a global problem and causes long-term disability in millions of individuals. This is a major problem for both military and civilian-related populations. The prevalence of sleep disorders in individuals with TBI is very high, yet mostly unrecognized. Approximately 46% of all chronic TBI patients have sleep disorders, which require nocturnal polysomnography and the Multiple Sleep Latency Test for diagnosis. These disorders include sleep apnoea (23% of all TBI patients), post-traumatic hypersomnia (11%), narcolepsy (6%) and periodic limb movements (7%). Over half of all TBI patients will have insomnia complaints, most often with less severe injury and after personal assault, and half of these may be related to a circadian rhythm disorder. Hypothalamic injury with decreased levels of wake-promoting neurotransmitters such as hypocretin (orexin) and histamine may be involved in the pathophysiology of excessive sleepiness associated with TBI. These sleep disorders result in additional neurocognitive deficits and functional impairment, which might be attributed to the original brain injury itself and thus be left without specific treatment.

Sleep Disorders in Patients with Traumatic Brain Injury: A Review

Background
Adenosine is generated in response to cellular stress and damage and is elevated in the lungs of patients with chronic lung disease. Adenosine signaling through its cell surface receptors serves as an amplifier of chronic lung disorders, suggesting adenosine-based therapeutics may be beneficial in the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Previous studies in mouse models of chronic lung disease demonstrate that the key components of adenosine metabolism and signaling are altered. Changes include an up-regulation of CD73, the major enzyme of adenosine production and down-regulation of adenosine deaminase (ADA), the major enzyme for adenosine metabolism. In addition, adenosine receptors are elevated.

/pdf/alterations-in-adenosine-metabolism-and-signaling-in-gnufmchkej.pdf

Alterations in Adenosine Metabolism and Signaling in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

THE DIAGNOSIS OF SLEEP APNEA TYPICALLY INVOLVES AN OVERNIGHT POLYSOMNOGRAM WITH CONTINUOUS MONITORING OF SEVERAL PHYSIOLOGIC parameters and surrogate measures of airflow (nasal pressure [Pn], oronasal thermistor, expired CO2 waveform [PECO2]) using contact sensors.1–5 A subject can come in contact with at least 20 such sensors during a study. These sensors and the wires can influence not only the usual sleep architecture, but also the posture of the patient during the study night.6–8 Contact sensors like nasal prongs and oronasal thermistors are routinely used as surrogate measures of airflow because they are less obtrusive than the reference-standard airflow sensor, namely, the pneumotachometer.1,9,10 However, the presence of the surrogate airflow sensors and the associated wires in the proximity of the subject's oronasal area can still cause discomfort to the patient during sleep. Contact sensors also have the potential to misalign during the study, requiring repositioning at the bedside by a technician, to obtain good-quality data.

We have demonstrated that measurement of breathing rates is feasible at a distance using thermal infrared imaging (TIRI).11 The method is based on second-order statistics of the presence or absence of the hot expiratory plume in the vicinity of the nostrils. We have also studied a more advanced method that is based on wavelet analysis of the thermal imaging signal on the nostrils themselves.12,13 When analyzing the thermal imaging signal, we extracted the full breathing waveform (rate and amplitude). Consistent segmentation of the nostril area and facial tissue-tracking algorithms14 enabled sustained monitoring of breathing, resulting in functionality equivalent to that of a thermistor, delivered in a contact-free manner. In 5-minute recordings of 20 awake healthy individuals, agreement between breathing waveforms from the virtual (imaging) and contact thermistors was found to be greater than 90%.

The hardware and software system that was developed to implement the latest method is called automatic thermal monitoring system (ATHEMOS). The centerpiece of the system is a midwave infrared camera (FLIR® SC-6000), supported by a black body for calibration and a pan-tilt mechanism for positioning. The system is controlled and the acquired imaging signals are processed by real-time custom software developed in our labs.

ATHEMOS and the imaging method that we reported on in a previous publication12 constitute the TIRI portion of the present study. The objective in this current study was to determine the efficacy of TIRI to detect apnea and hypopnea by using conventional surrogate airflow sensors as comparison standards during polysomnography. Thus, our hypothesis was that there would be a very high degree of chance-corrected agreement (κ ≥ 0.6) between TIRI and each of the conventional flow sensors, such as thermistor, Pn, and PECO2 in the detection of apnea and hypopnea. Some of the data from this manuscript has been presented at scientific meetings and published in the form of abstracts.15,16

/pdf/thermal-infrared-imaging-a-novel-method-to-monitor-airflow-v0mpwu4uql.pdf

Thermal infrared imaging: a novel method to monitor airflow during polysomnography.

There are ~12,000 new cases per year in the United States of spinal cord injury (SCI) with life expectancies from 11 to 14 years (ventilator dependent) to 44 years (non-ventilator dependent). Those with SCI (C2-C8) are at great risk for developing hypoventilation, especially during sleep, and this risk increases along with the risk of sleep disordered breathing as they age. Most will have significantly reduced vital capacity and ventilatory reserve because of interruption of neural pathways to the diaphragm, chest, and abdomen, resulting in a restrictive ventilatory impairment with intact diffusing capacity. Diagnosis entails measurement of pCO (2) with capnography both awake and during sleep, optimally along with polysomnography to evaluate for all forms of sleep disordered breathing. Treatment options include diaphragmatic pacing, full positive pressure ventilation through tracheostomy, and noninvasive positive pressure ventilation. Some may require mechanical ventilation only during sleep.

Jayasimha N. Murthy

Papers

The six minute walk test accurately estimates mean peak oxygen uptake

Sleep Disorders in Patients with Traumatic Brain Injury: A Review

Alterations in Adenosine Metabolism and Signaling in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

Thermal infrared imaging: a novel method to monitor airflow during polysomnography.

Hypoventilation after spinal cord injury.