**2.1. EFL in chronic obstructive pulmonary disease (COPD) and asthma**

Fifty years ago, Hyatt (1961) suggested that patients with severe COPD may exhibit expira‐ tory flow limitation (EFL) at rest. This phenomenon could be demonstrated by the finding that they breathed tidally along or above their maximal expiratory flow-volume curves. This pattern of tidal breathing leads to hyperinflation, increased work of breathing, impaired res‐ piratory muscle function, hemodynamic compromise (Gottfried, 1991), and dyspnea (El‐ tayara et al., 1996; O'Donell et al., 1987). A high prevalence of tidal EFL is found in patients with COPD (Baydur et al., 2004; Gottfried et al., 1991; Hyatt et al., 1961) (Figure 5). As many as one-third of patients were flow-limited in seated and supine postures in the report of Baydur et al. (2004). A smaller percentage of patients with asthma in remission exhibit EFL, almost always in the supine posture (Baydur et al., 2004; Boczkowski et al., 1997).

flow-volume curves (Beck et al, 1991; Grimby & Stiksa, 1970; Hyatt, 1961; Kosmas et al., 2004; Koulouris, 1997; Murciano et al., 2000; Stubbing et al., 1980; Younes & Kivinen, 1984). Patients with EFL exhibit progressive lung inflation, increased sensation of dyspnea, and re‐

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Manual compression of the abdominal wall has also been used to detect EFL (Ninane et al., 2001). It has the advantage of generating an increase in abdominal pressure (of about 15 cm H2O) that results in cranial displacement of the diaphragm into the thorax (provided it is re‐ laxed) and a rise in pleural pressure (of about 6 cm H2O) without the use of a special device. It also does not depend on previous volume and time history, and relies on a modest in‐ crease in alveolar pressure rather than a vacuum applied at the mouth, thus avoiding arti‐ fact caused by upper airway collapsibility. One study of this maneuver resulted in an increase in tidal expiratory flow in normal subjects, while it exhibited EFL in half of 12 pa‐ tients with COPD in both supine and seated postures, and in 4 additional patients in supine

Expiratory flow limitation is more prevalent in the elderly and is related to the severity of dyspnea (de Bisschop et al., 2005). In general, EFL does not closely correlate with FEV1 or FEV1/FVC (Eltayara et al., 1996). Older dyspneic individuals without cardiorespiratory dis‐ orders tend to be more flow limited than non-dyspneic persons (de Bisschop et al., 2005).

In individuals with restrictive disorders (particularly those with infiltrative disorders, such as idiopathic pulmonary fibrosis) maximal expiratory flows are well preserved despite a marked decrease in lung volume (Bergofsky, 1995). Consequently, breathing occurs at low lung volumes (near residual volume) where maximal expiratory flows are relatively small. Furthermore, some patients with interstitial lung diseases exhibit a decrease in dynamic compliance with breathing frequency (Bergofsky, 1995; Fulmer et al., 1977). In some of these patients, including non-smokers, flow rates are reduced with respect to transpulmonary pressure (Fulmer et al., 1977; Gaultier et al., 1980; Murphy et al., 38). Baydur et al. (1997, 2004) did not find any patients with restrictive disorders who exhibited intrathotracic EFL in either body position. The absence of EFL can be attributed to the increase in elastic recoil associated with these disorders. Others, however, have described the presence of EFL in pa‐ tients with cardiac failure (Duguet et al., 2000), acute respiratory distress syndrome (Kout‐

**2.3. EFL in sleep apnea; differences in FL pattern from COPD and asthma as assessed by**

The NEP technique has also been used to assess upper airway collapsibility in patients with OSA, in which EFL has been described as a transient or sustained decrease in expiratory flow (frequently below the control tidal expiratory flow) during application of NEP (Baydur et al., 2004; Liistro et al., 1999; Van Meerhaeghe et al., 2004; Verin et al., 2002) (Figure 7).

duced maximal oxygen uptake during exercise.

position alone (Ninane et al., 2001).

**the NEP method**

**2.2. EFL in restrictive respiratory disorders**

soukou et al., 2000), and pleural effusions (Spyratos et al., 2007).

The NEP technique can be used to advantage in young children unable to perform forced expiratory volume maneuvers (Braggion et al., 1998; Goetghebeur et al., 2002; Jiřičkova et al., 2009; Jones et al., 2000; Tauber, et al., 2003). Goetghebeur et al [10] described EFL in chil‐ dren aged older than 12 years with cystic fibrosis. These patients exhibited markedly de‐ creased inspiratory capacity (IC) and forced expiratory volume at 1 sec (FEV1). The NEP technique has also been used to evaluate EFL in infants (Braggion et al., 1998; Jiřičkova et al., 2009; Jones et al., 2000). Jiřičkova et al. (2009), applying the NEP technique in newborns and pre-school children, found nearly half of their patients to be intrathoracically flow-limited. The same number of children, however, exhibited transient upper airway collapse (UAC). The authors did not specify, if in some children, the UAC may have obscured any underly‐ ing intrathoracic EFL (see below).

An advantage of using the NEP technique in the evaluation of intrathoracic EFL is the avoidance of variability in the forced expiratory vital capacity maneuver related to the pat‐ tern of inspiratory maneuver preceding forceful expiration. Fast inspiration followed imme‐ diately by forced expiration results in greater forced vital capacities (FVC) and peak expiratory flows (PEF) by generating higher elastic recoil; in contrast, performing a breath‐ hold between inspiration and expiration diminishes elastic recoil and results in lower FVC and PEF. This finding, observed in both in healthy volunteers (D'Angelo et al., 1993; Tzele‐ pis et al., 1997; Wanger et al., 1996) and patients (Braggion et al., 1996; D'Angelo et al., 1994; D'Angelo et al., 1996; Wanger et al., 1996), has been ascribed to the viscoelastic properties of the lung (D'Angelo et al., 1991) and to greater activation of expiratory muscles (Tzelepis et al., 1997) occurring with fast maneuvers. The NEP method also avoids underestimation of lung volumes during rapid expiratory maneuvers due to gas compression (Ingram & Schil‐ ler, 1966; Koulouris et al., 1995).The technique also avoids incorrect alignment of the tidal and maximal expiratory flow–volume curves. Such alignment is usually made considering the total lung capacity (TLC) as a fixed reference point, and this assumption may not always be valid (Kosmas et al., 2004; Koulouris, 1997; Murciano et al., 2000).

The NEP technique has also been used to detect EFL during exercise (Koulouris et al., 1997). In normal young subjects, there is no evidence of EFL during submaximal exercise. By con‐ trast, most patients with COPD exhibit NEP-generated EFL during light exercise. These findings are in agreement with exercise studies employing conventional forced expiratory flow-volume curves (Beck et al, 1991; Grimby & Stiksa, 1970; Hyatt, 1961; Kosmas et al., 2004; Koulouris, 1997; Murciano et al., 2000; Stubbing et al., 1980; Younes & Kivinen, 1984). Patients with EFL exhibit progressive lung inflation, increased sensation of dyspnea, and re‐ duced maximal oxygen uptake during exercise.

Manual compression of the abdominal wall has also been used to detect EFL (Ninane et al., 2001). It has the advantage of generating an increase in abdominal pressure (of about 15 cm H2O) that results in cranial displacement of the diaphragm into the thorax (provided it is re‐ laxed) and a rise in pleural pressure (of about 6 cm H2O) without the use of a special device. It also does not depend on previous volume and time history, and relies on a modest in‐ crease in alveolar pressure rather than a vacuum applied at the mouth, thus avoiding arti‐ fact caused by upper airway collapsibility. One study of this maneuver resulted in an increase in tidal expiratory flow in normal subjects, while it exhibited EFL in half of 12 pa‐ tients with COPD in both supine and seated postures, and in 4 additional patients in supine position alone (Ninane et al., 2001).

Expiratory flow limitation is more prevalent in the elderly and is related to the severity of dyspnea (de Bisschop et al., 2005). In general, EFL does not closely correlate with FEV1 or FEV1/FVC (Eltayara et al., 1996). Older dyspneic individuals without cardiorespiratory dis‐ orders tend to be more flow limited than non-dyspneic persons (de Bisschop et al., 2005).
