Impaired exercise ventilatory efficiency in smokers with low transfer factor but normal spirometry

Cardiopulmonary and Muscular Interactions: Potential Implications for Exercise (In)tolerance in Symptomatic Smokers Without Chronic Obstructive Pulmonary Disease

“…It is also plausible that increased chemo-stimulation as a result of higher physiological dead space (increased V′E/V′CO 2 , ventilatory inefficiency) contributes to a higher inspiratory neural drive during tidal breathing in some smokers (Elbehairy et al, 2016; Weatherald et al, 2018). Increased V′E/V′CO 2 , likely reflecting high VD/VT, was found in smokers with only mild spirometric abnormalities (Elbehairy et al, 2017a,b) and smokers with low lung diffusion capacity for CO (Walter Barbosa et al, 2017). Importantly, a large populational study found that, after careful control for confounders, chronic cigarette smoking was associated with increased alveolar-arterial gradient and dead space on exercise (Gläser et al, 2010, 2013).…”

“…In this context, reduced maximal and submaximal exercise tolerance and breathlessness on daily life (modified Medical Research Council dyspnea score, ≥2) have been described in a subgroup of smokers, even when they do not fulfill the extant physiological criteria for COPD (Klein et al, 1992; Misigoj-Durakovic et al, 2012; Liu et al, 2015; Regan et al, 2015; Elbehairy et al, 2016, 2017a; Woodruff et al, 2016; Di Marco et al, 2017; Martinez et al, 2017; Walter Barbosa et al, 2017; Fuertes et al, 2018) and they are not particularly sedentary (Misigoj-Durakovic et al, 2012; Fuertes et al, 2018). It is widely accepted that exercise intolerance is the final result of abnormalities in the complex interaction between large systems (mainly pulmonary and cardiocirculatory) which support O 2 delivery to muscle mitochondria (Burtscher, 2013; Gabriel and Zierath, 2017).…”

“…Oxygen (O 2 ) transport disturbances [including high blood carboxy-hemoglobin levels (HbCO); Huie, 1996; Maehara et al, 1997; Bye et al, 2008; Barn et al, 2018] and, potentially, cardiocirculatory abnormalities (Gidding et al, 1995; Lauer et al, 1997; Bernaards et al, 2003; Kobayashi et al, 2004; Tello et al, 2005; Papathanasiou et al, 2007), and autonomic nervous system unbalance (Kotamäki, 1995; Mendonca et al, 2011; Ide and Tabira, 2013). Of note, influential reviews on the topic (Huie, 1996; Heishman et al, 2010) did not consider the modulatory effects of abnormalities that only recently have gained more attention, including early emphysema (Sashidhar et al, 2002; Fain et al, 2006; Grydeland et al, 2009; Harris et al, 2012; Mohamed Hoesein et al, 2014; Regan et al, 2015; Alcaide et al, 2017; Crossley et al, 2018), pulmonary microvascular disease (Nana-Sinkam et al, 2007; Schweitzer et al, 2011; Harris et al, 2012; Estépar et al, 2013; Schmekel et al, 2013; Iyer et al, 2016; Rizzi et al, 2016; Aaron et al, 2017, 2018; Saruya et al, 2017), ventilatory inefficiency, (Gläser et al, 2011; Elbehairy et al, 2016; Walter Barbosa et al, 2017), gas exchange abnormalities (Gläser et al, 2010, 2011, 2013; Elbehairy et al, 2015), and left ventricular diastolic dysfunction (Tello et al, 2005; Payne et al, 2006; Gulel et al, 2007; Yilmaz et al, 2007; Bennet et al, 2010; Talukder et al, 2011; Leary, 2016; Nadruz et al, 2016).…”

“…In fact, some smokers do experience a larger-than-expected (by aging) decrease in maximal O 2 consumption (V′O 2max ) (0.2–0.5 mL × min −1 × kg −1 /year) (Burtscher, 2013; Roman et al, 2016; Rodrigues et al, 2018), an effect that might be, at least in part, genetically determined (Ross et al, 2018). Thus, there is growing evidence in favor of derangements in the muscle-lung-heart axis (Bye et al, 2008; Grydeland et al, 2009; Gläser et al, 2013; Degens et al, 2015; Regan et al, 2015; Leary, 2016; Alcaide et al, 2017; Saruya et al, 2017; Walter Barbosa et al, 2017; Barn et al, 2018) that may have sensory consequences and contribute to poor exercise tolerance in ever-smokers or former smokers without COPD (Figure 1, above). Overall, these derangements are followed by clinical traits increasingly described in the medical literature (Figure 1, below).…”

Ventilatory inefficiency during graded exercise in COPD: A pragmatic approach

“…To test this new approach, thirty COPD patients (GOLD stage II‐IV; ten subjects per stage) were compared with ten individuals at risk for COPD (smokers with reduced DLco, peripheral airway obstruction or clinical symptoms of cough or dyspnoea, but actual postbronchodilator FEV 1 /FVC > 70% predicted and FEV 1 > 80% predicted) retrospectively from our database (Walter Barbosa et al, 2017), for lung function tests and cardiopulmonary exercise testing, including V ´ E ‐V ´CO 2 slope, V ´ E ‐V ´CO 2 nadir, V ´ E ‐V ´CO 2 intercept, CO 2 ‐ ACR, and ηV ´ E as endpoints.…”